Histometric components of aortic atherosclerosis which vary or remain constant among eight populations

In the objective examination of aortic histology, each position observed in a sample can be classed as having or not having atheronecrosis, and each aorta can be scored as affected in a measured percentage of the sample. Positions not having necrosis can be measured for intimal thickness and the mean of those measurements is an estimate of the quantity of intimal fibroplasia. Both atheronecrosis and fibroplasia, measured in these ways, increase with age. Within age groups these two variables are correlated with each other. By multivariate statistical methods, independent variation of the two variables among populations was assessed. Populations compared were from Bogota, Durban (Bantu and Indian), Manila, Mexico, New Orleans (Negro and White) and Sao Paulo. Manila ranked highest on the quantity of fibroplasia and Durban Bantu lowest. Sao Paulo ranked highest on the extent of atheronecrosis and New Orleans Negro was lowest. The two variables assorted among the eight populations independently of each other to a large degree, suggesting that fibroplasia and atheronecrosis are at least in part subject to separate and independent causes. The numbers of smooth muscle cells and the extent of foam cell infiltration did not differ significantly between atherosclerosis related and basal cause of death groups. These cellularity measures were, with minor exceptions, not significantly different among populations, suggesting that they are inherent human characteristics largely unaffected by environmental circumstances.     

Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities.

A comparative morphologic study of aortic changes with aging was conducted in different populations in an attempt to separate the effects of hypertension and atherosclerosis. Chinese and the occidental populations were chosen, as they are known to have a high prevalence of hypertension and atherosclerosis, respectively. Aortic tissue was collected from occidental (American and Australian) and Chinese populations from three geographic locations. Postmortem specimens were obtained from four fixed locations: ascending aorta (A), descending thoracic aorta (B), and abdominal aorta (suprarenal [C] and above the aortic bifurcation [D]). Histologic sections were used to measure aortic circumference, medial thickness, intimal thickness, and grade of atherosclerosis. Kidney sections were used to confirm the presence or absence of hypertension. A total of 302 cases (age range, 19 to 104 years; Male-to-female ration, 2:1) were studied: 112 Americans, 80 Australians, and 110 Chinese. Cases were divided into three age groups: 19 to 44; 45 to 64; and 65 years and older. The aortic circumference progressively decreased from sites A to D in all populations and age groups. The aortic circumference increased with age, and the increase was independent of the aortic location. When the populations were separated, however, the greater increase was at location A in the Chinese (P = .008) and locations D in the occidental (P = .13), a population contrast that was significant only in location A. Intimal thickness increased with advancing age and was maximal in the abdominal aorta. The population differences also were significant for intimal thickness and were significantly greater in the occidental population in B, C, and D locations, whereas for atherosclerosis significance was only seen in location D. Hypertension (as defined by the morphologic changes in the kidney) after adjusting for age, height, and weight resulted in no statistical significant effect on aortic circumference or on intimal thickness, but did show a significant increase in atherosclerosis score at locations B, C, and D. Also after adjusting for age, height, and weight, the Chinese had a significantly larger aortic circumference in location A compared with the occidental population, whereas in location D the occidentals with hypertension had a significantly larger circumference compared with Chinese, probably due to an interaction of atherosclerosis and hypertension. After similar adjustments, the medial thickness in locations A and C, the intimal thickness in B, C, and D, and atherosclerosis score in D were significantly greater in occidental than Chinese populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Spatial dispersion of stainable lipid in frozen sections of human aorta

Summary Frozen sections of human lateral thoracic aorta were stained for lipid with Oil red O. Intensity of staining was judged upon a scale of 0 to 5 brilliance units by matching to a scale of photographs. Microregions, defined by an eyepiece grid, were structured in layers of 100 µm thickness and 1000 µm along the aortic length. The intensity of staining, both total and extracellular, tended significantly to increase with age, intimal thickness and depth into the intima. Aortas having at least one instance of atheronecrosis tended to show generally greater staining intensities than aortas without necrosis, and the tendency was more conspicuous with total than with extracellular staining, implying a greater degree of intracellular staining in the specimens with atheronecrosis. The evidence seems to suggest that the emergence of a necrotic core happens, at least in part, because the affected site has collected an excess of lipid. The evidence further suggests that lipid deposits become excessive with increasing frequency after age 35 years, and that this is associated with intimal thickenings coming to exceed 300 µm. The causes that propel the intimal thickenings remain wholly unknown- those causes seem to have little if anything to do with excess of lipids. Some as yet undetermined qualitative characteristic of the lipids might be of importance in this regard.     

Vascular smooth muscle cells of recipient origin mediate intimal expansion after aortic allotransplantation in mice

Intimal expansion by vascular smooth muscle cells (SMCs) is a characteristic feature of graft vascular disease. Whether graft intimal SMCs arise from donor or recipient tissue is not well established but has important pathogenetic implications. We examined for the presence of male cells in the expanded intima of sex-mismatched mouse aortic allografts (C57BL/6-to-BALB/c) at 30 or 60 days after transplant by in situ hybridization using a Y-chromosome probe. Study groups included male-to-female allografts, female-to-male allografts, and female-to-female allografts in recipients previously engrafted with male bone marrow. Although intimal expansion developed in all allografts, male-to-female allografts lacked Y-chromosome-positive intimal cells. In contrast, such cells were abundant in female-to-male allografts and most of these cells co-labeled for smooth muscle alpha-actin by immunostain. Female-to-female allografts in recipients with male bone marrow showed a limited number of intimal Y-chromosome-positive cells. However, none of these clearly co-labeled for smooth muscle alpha-actin and their numbers declined throughout time, consistent with graft-infiltrating inflammatory cells. We conclude that intimal expansion of mouse aortic allografts is mediated by SMCs that originated from the recipient. There was little evidence of their derivation from the bone marrow, suggesting instead the adjacent host aorta as the primary source of intimal SMCs.     

Sequestration hypothesis of atherosclerosis

Summary Atherosclerosis of the human aorta has been studied by morphometric, chemical, and histochemical methods. Results of these separate approaches are converging upon a theory of pathogenesis. This theory begins with the standard view of a two stage process, intimal fibroplasia followed by atheronecrosis in the most thickened and aged places. The first stage, fibroplasia, can be described in terms of a stochastic process wherein smooth muscle cells, scattered in accordance with a Poisson distribution, elaborate matrix materials over time, causing the realms of the cells to expand and to aggregate. The fusion of the expanded smooth muscle cell realms seems to mark the advent of necrosis. The second stage, atheronecrosis, can be described such that the probability of a necrotic core emerging at a site in a vessel is governed by the amount and the age of interstitial matrix materials at the site. Further evidence shows that the matrix materials tend to sequester lipids in greater than proportionate amounts as the intimal bulk increases. The sequestered perifibrous lipid is histochemically different from the lipids of the necrotic core, in that only the latter can be fixed with chromic acid. These results suggest that lipids undergo a qualitative change as well as a quantitative increase at the stage of impending necrosis. This qualitative change is governed by age, which raises the possibility that necrotizing toxicity accumulates in the sequestered lipid as it ages.     

Population dynamics of arterial cells during atherogenesis. IX. Similarity of endothelial cell loss over intimal smooth muscle cell masses (cushions) in aortas of swine fed normolipidemic and hyperlipidemic diets for 60 days.

The objective of this study was to ascertain whether the previously demonstrated increased endothelial cell loss over swine aortic intimal cell masses (cushion areas) was dependent on a hyperlipidemic diet being fed to the swine. Aortic endothelial cells were labeled with tritiated thymidine. Fifteen swine were placed on a lowcholesterol (mash) diet for 15 days, at which time five were sacrificed for baseline studies. Five of the remaining swine were continued on the mash diet while five were placed on a hyperlipidemic diet; these two experimental groups were killed on Day 75 of the experiment. The rate of endothelial cell growth, division patterns, and loss of labeled endothelial cells over intimal cell mass and non-intimal cell mass areas were calculated in the two groups by comparing the findings in these groups to the baseline group. While endothelial cell loss was greater over aortic intimal cell mass areas than over other parts of the aorta, the hyperlipidemic diet did not enhance this during the period of study. Endothelial cells were lost at a similar rate over intimal cell mass areas in both the normolipidemic mash group and the hyperlipidemic group. The hyperlipidemic diet did, however, produce a significant increase in the surface area of aorta occupied by intimal cell mass areas, presumably due to the effect of the diet on smooth muscle cells. The endothelial cells covering these areas also increased significantly in number. The increase was brought about by an increase in the number of dividing endothelial cells which more than equaled a decrease in the average number of progeny per endothelial cell.     

The action of aging upon coronary intima and renal microvasculature in USA and Andes populations.

Full lengths of right coronary artery obtained at autopsy and examined in hematoxylin and eosin stained paraffin sections sometimes reveal the presence of at least one instance of atheroma (YesA specimens). YesA specimens are nearly always those with generalized intimal fibroplasia, measured by excessive intimal thickness per smooth muscle cell. Accumulating evidence suggests that aging governs the progression of fibroplasia, and that this fibroplasia is what aging does to the coronary artery in preparation for atheroma. Hyalinization of renal arterioles was previously found to correlate strongly with the presence of coronary atheroma and with the progression of the fibroplasia of aging in race, sex, age matched comparisons of subjects within a population (forensic autopsies in New Orleans). The data reported here reveal the correlation of arteriolar hyalinization with fibroplasia and atheroma to persist in comparisons across geographically diverse populations. The outcome suggests that aging of coronary intima, in so far as it bears upon preparation for atheroma, may vary in rate between populations. This source of variation could offer clues about environmental factors that may modify rates of aging.     

Rapidly progressive atherosclerosis in aortocoronary saphenous vein grafts. Possible immune-mediated disease

One hundred fifteen aortocoronary saphenous vein grafts from 100 consecutive reoperations were examined. Ninety-nine percent of the grafts contained diffuse concentric intimal fibroplasia. Forty-six percent of the grafts were atherosclerotic. The atherosclerosis was typically rapid in development, concentric, diffuse, without a fibrous cap, with numerous foam cells and inflammatory cells, including multinucleate giant cells, with erosion of the media by the inflammatory reaction. The histologic features of the grafts were similar to those reported in experimental models of immune-mediated atherosclerosis. On this basis we propose that aortocoronary saphenous vein graft atherosclerosis, and possibly intimal fibroplasia, may be an immune-mediated disease.     

A MORPHOLOGICAL STUDY OF DISSECTING ANEURYSM OF AORTA IN OLD INDIVIDUALS OVER 50 YEARS OF AGE

The authors have Investigated the pathogenesis of dissecting aneurysms morphologically in 49 cases over 50 years of age, using 93 cases of other diseases in the same age group as control cases. All cases were autopsied at the Tokyo-to Medical Examiner Office. The dissecting aneurysms were divided into two types: one type occurred chiefly at the ascending aorta where atherosclerosis was missing or slight, and the other type chiefly at the descending aorta with severe atherosclerosis of the intima. In the former type, intimal tears were recognized in all cases and microscopically in the neighboring area of the cleft of aortic wall vacuolous large cyst without accumulation of metachromatic ground substance. Near the cyst, elastic lame llae were destroyed and the vasa vasorum was generally thickened, and multiple dissecting hemorrhages were observed. In the latter type, even when the intimal tears were not obvious, microscope revealed crumbled atheroma and bleeding in the intima or bleeding within the atheroma. The dissecting bleeding continued from it. Moreover, since enlargement of heart was observed in most cases, hypertension was thought to be an important factor among the predisposing factors in the pathogenesis of dissecting bleeding of the aorta.     

Arrhythmic sudden cardiac death in a 3-year-old child with intimal fibroplasia of coronary arteries, aorta, and its branches.

We report an unusual case of "arrhythmic" sudden cardiac death in a 3-year-old child who died of ischemic myocardial lesions as a result of intimal fibroplasia of the coronary arteries. Also affected were the aorta and its major branches, whereas renal and mesenteric arteries, celiac trunk, and systemic veins were normal. Histopathologic examination showed severe concentric thickening of intima because of a proliferation of spindle-shaped cells (mesenchymal cells) set in an abundant extracellular matrix. In some vascular segments the intima was densely fibrotic and hyalinized. No significant inflammation, foam cells, cholesterol clefts, or other evidence of atheroma were present. The intimal lesions did not involve the media and/or the adventitia. Immunohistochemical staining of intima showed the proliferating mesenchimal cells to be myofibroblastic. Reactions for vimentin and smooth muscle actin were positive, while those for desmin, myosin, CD34, and Factor VIII were negative.     

Intimal thickening involves transdifferentiation of embryonic endothelial cells

Morphological studies have hypothesized different origins for the precursors of the vascular smooth muscle cells (SMCs). The intriguing possibility that intimal SMCs may arise from the endothelium has newly emerged. As a first step towards understanding of the possible mechanisms involved in the transdifferentiation of endothelium into smooth muscle cells, we characterized the in vivo phenotype of the cells located in the aortic wall (distal to the aortic arches). This was accomplished using advanced stages of chicken embryo development. Furthermore, we investigated whether the cells present at the intimal thickening derive from the endothelial cell transdifferentiation. Immunolabeling of serial cryosections suggested that mesenchymal cells observed in the intimal thickening may arise from the endothelium. These cells may persist either as non-muscle throughout the development or possibly convert to cells expressing smooth muscle alpha-actin (SM alpha-actin). To determine whether endothelial cells may actually transdifferentiate into mesenchymal cells, aortic explants from 14-day-old chicken embryos (stage 40) were used. We found that explanted endothelial cells lose their cobblestone-appearance and migrate toward cell-free area. Some of these cells maintain the vWf immunoreactivity, whereas other cells coordinately lose vWf and gain SM alpha-actin expression (transitional cells). Taken together these findings strongly support the possibility that embryonic aortic endothelial transdifferentiate into mesenchymal cells, some of which express SM alpha-actin. Since TGFbeta-3 is considered an essential factor during epithelial to mesenchymal transitions in earlier chicken heart development, we also investigated the distribution of this growth factor at day 14. Our observations indicated that the immunoreactivity for TGFbeta-3 in this stage may be associated with migrating mesenchymal cells and that this immunoreactivity appears to decrease as cell differentiation advances. Therefore, the present study provides evidence that could help to explain 1) the presence of cells displaying a phenotype reminiscent of fetal-like cells in the normal chicken aorta and in the intimal region of the human aorta; 2) the SM lineage diversity in the chicken embryo reported by others; 3) a subpopulation of immature cells in the subendothelial region of the main pulmonary arteries of fetal, neonatal and adult bovines; and 4) the presence of intimal cushions, intimal pads, eccentric and diffuse intimal thickening that are observed in mammalian and avian vessels at birth.     

Intimal thickness and layering, and smooth muscle cell phenotypes in aorta of youth.

Proneness to the lesions of atherosclerosis varies along the length and circumferential topography of the aorta. Smooth muscle cells, in particular those of the 'modulated' synthetic phenotype which are able to proliferate and synthesize matrix proteins, are considered to play an important role in lesion progression. We report on a study of the aortic intima at a lesion-prone site from abdominal aorta and a lesion-resistant site from thoracic aorta in young humans to determine (1) whether the histologic structure and the smooth muscle cell composition show quantitative differences between lesion-prone and lesion-resistant aortic sites; (2) whether there are gender differences, and (3) whether any differences increase in degree with increasing age in this young population. Material for this study was obtained as part of the NIH-funded multicenter study on Pathobiological Determinants of Atherosclerosis in Youth (PDAY) from autopsies of male and female subjects between the ages of 15 and 34, victims of unexpected sudden death, usually from trauma. The samples consisted of strips of abdominal and thoracic aorta, all derived from the same anatomical sites standardized in the PDAY studies. The thickness of total intima (TI) and its elastic hyperplastic (EH) layer was measured. Smooth muscle cells of all types (SMC) and separately those of the synthetic phenotype (SynSMC) were quantified in each site using immunohistochemical procedures in replicate sections of uniform thickness. The intima of the atherosclerotic lesion-prone dorsal half of the abdominal aorta (AD) shows significant differences from the lesion-resistant ventral half of thoracic aorta (TV) in that (1) its EH layer is significantly thicker; (2) its EH layer has a comparatively higher number of both total SMC and SynSMC, even when adjusted for intimal thickness, and (3) the age-related increase in thickness of both TI and EH layer of AD is much greater than that of TV.     

Ultrastructural localization of peroxidase in atherosclerotic lesions of pigeons.

Atherosclerotic lesions are known to have metabolic alterations which are associated with progressive lipid accumulation. Among the changes, lysosomal enzyme activity has been extensively characterized and at the ultrastructural level has been correlated with the amount of foam cell lipid. In a fashion paralleling lysosomal change, artery wall peroxidase activity is also altered during disease progression. The present study focuses upon the ultrastructural localization of peroxidase activity in atherosclerotic lesions of the aorta and coronary arteries from White Carneau pigeons fed a cholesterol-supplemented (0.3%) diet for 3 years. This resulted in fibrous lesions, rich in smooth muscle cells. The birds were necropsied by perfusion fixation, and peroxidase cytochemistry was carried out using the diaminobenzidine reaction. Peroxidase activity was found within endothelial cells and smooth muscle cells in both the media and intima, but cytochemically demonstrable activity was not found in macrophage foam cells. Peroxidase was localized within the nuclear envelope and endoplasmic reticulum, especially within cells that had lipid inclusions. The degree of peroxidase positivity varied within and among the arteries. In nonlesion regions of the aorta 20% of medial smooth muscle cells was peroxidase positive; the value for coronary artery smooth muscle cells was less. The peroxidase activity within aortic lesions was increased with 44% of intimal smooth muscle cells being positive. Notably, 85-90% of the lipid-containing intimal smooth muscle cells were positive. In contrast, intimal smooth muscle cells in the coronary artery lacked peroxidase reaction product, even in cells containing lipid. We conclude from these studies that aortic lesions contain a cytochemically differentiated subset of lipid-containing, peroxidase-positive smooth muscle cells; but coronary lesions lack a comparable subset of smooth muscle cells.     

Endothelin. Immunohistologic localization in aorta and biosynthesis by cultured human aortic endothelial cells.

BACKGROUND: Endothelin-1 (ET-1) has been shown to exist in many organs and to have various biologic functions including vasoconstriction. However, an exact location of ET gene expression of the tissues is not fully investigated. Human aortic tissue was examined to elucidate the exact location of ET gene expression. EXPERIMENTAL DESIGN: Human aortas were obtained at autopsy and fixed in either conventional 10% formalin or 3% paraformaldehyde. The aortic thin sections were subjected to examinations of an immunohistochemistry and in situ hybridization of ET-1. Human aortic endothelial cells were cultured by a previously reported method. ET-1 released in the supernatant from the cultured endothelial cells was radioimmunoassayed. RESULTS: Immunohistologic study of ET-1 revealed a linear staining of the endothelial monolayer and diffuse staining in the intimal and medial smooth muscle cells on human aorta except for fetal aorta. In situ hybridization signals were intense in the endothelial cells from the elderly as well as younger subjects as examined with 35S-labeled anti-sense probe RNA. Fetal aortic endothelial cells revealed the least signals that meant developing but still immature gene translation. Smooth muscle cells showed positive but weak in situ hybridization signals. Control immunohistologic and hybridization studies were negative. ET-1 biosynthesis by cultured human aortic endothelial cells was invariably low in the subjects under the age of 50, ranging from 0.23 to 0.40 pmol/1 x 10(5) cells for 3 days. On the other hand, endothelial cells from the elderly subjects generally synthesized a greater amount of endothelin in vitro. CONCLUSIONS: These findings indicate that ET-1 is most highly expressed in endothelial cells, although not as highly but certainly, expressed in intimal and medial smooth muscle cells. This fact gives a new insight into the biophysiologic and pathologic roles of ET. In addition, these methods are applicable to investigate the gene expression of ET-1 in all organs and tissues.     

Surgical pathology of chronic ascending aortic dissections

AIMS: A majority of aortic dissections affect the ascending aorta and are acute in nature. Chronic dissections in this region are uncommon. This report characterises the clinicopathological features of 15 non-iatrogenic chronic ascending aortic dissections. METHODS: Among 65 patients who had surgery for ascending aortic dissection over a period of 6 years, 15 showed morphological evidence of chronic dissection. Clinical data and morphological features of these were analysed. RESULTS: Twelve patients (80%) were over the age of 50 years, with a male predominance (11 patients, 73.33%). Exertional dyspnoea was the most common presenting symptom, while chest pain was noted in three cases. An echocardiographic diagnosis of dissection was made in six patients. The disease was restricted to the ascending aorta in nine (60%) and all had aortic regurgitation of varying severity. Areas of recent dissection were also noted in three specimens. The risk factors or pathogenetic mechanisms noted were hypertension in four and Marfan's syndrome, penetrating atherosclerotic ulcer, patent ductus arteriosus, and vehicular accident, in one patient each. The aortic segment of the latter patient had shown intimal flaps to be associated with multiple saucer-shaped depressions with thin walls. These features were also noted in two of the seven patients without risk factors and in two hypertensives. This raises the possibility of subclinical intimal injury sustained during sudden deceleration with blunt chest trauma. Significant aortopathy was seen in 10 cases. CONCLUSIONS: Chronic dissections as a cause of aortic regurgitation and aneurysmal dilatation, especially in the elderly, should be kept in mind. This may follow sudden deceleration intimal injuries, superimposed on aged-related medial degeneration.     

Comparisons of human populations for histologic features of atherosclerosis. A summary of questions and methods for geographic studies

Aortas and coronary arteries from six populations were studied histologically. Two kinds of fibrous plaques could be defined morphometrically, a fibroplastic and an atheronecrotic kind. These two kinds of abnormality were quantitated, the percentage of the specimen affected by atheronecrosis being one quantity, and the average fibroplastic thickness of nonnecrotic intima being the other. These two quantities were found to be correlated with each other, showing that aortas or coronary arteries severely affected by one of these processes tended to be seriously affected also by the other process. This correlation persisted after age adjustment. The two processes, however, failed to parallel each other across population boundaries. Moreover, some of the subjects with coronary heart disease had excessive fibroplasia with minimal atheronecrosis, while others had excessive atheronecrosis with minimal fibroplasia, as if an excess of only one or the other can be fatal. A novel theory is proposed to explain these and other results. It is proposed that the arterial intima undergoes fibroplastic thickening under the time-dependent action of one set of hypothetical causes and that another set of hypothetical causes promotes the emergence of atheronecrosis in the most thickened and aged places. These two sets of causes appear to be independent of each other in their distribution among human populations.     

Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli

A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor.     

Declining density of intimal smooth muscle cells and age as preconditions for atheronecrosis in the basilar artery

The aging basilar artery has some differences and some similarities when compared with the aorta and coronary arteries. As the non-necrotic intimal thickness increases over time, the number of smooth muscle cells reaches a steady state around age 25–30 years in the coronaries and aorta, but continues to increase in the basilar artery, even to 90 years of age. The numbers of cells per unit of tissue (the cell density) declines with age, and the patterns of decline are quantitatively similar in all three arterial segments. All arteries so far examined behave alike in showing that atheronecrosis emerges in those specimens that have sufficiently low density of intimal smooth muscle cells. These results identify low intimal cell density as a criterion for recognizing arteries that are prone to atheronecrosis. One possible explanation is that depopulation of the fibrotically thickened and aged intima, by spreading apart the smooth muscle cells with expanding matrix materials, could be the conditioning factor that brings about the intrusion of atheronecrosis.     

Caprine arterial diseases. I. Spontaneous aortic lesions

The spontaneous aortic lesions reported are based on the examination of 1325 aortas of goats, aged 1.5–4 years. The aortic lesions were observed in 64.26% animals. Based upon the gross and histopathologic findings, these lesions have been categorized as fatty spots/streaks (51.45%), intimal elevation (0.77%), intimal corrugation (0.77%), focal intimal thickening (0.05%), fibrous plaque (10.30%), aortitis media (0.39%), and aneurysm (0.53%). The fatty spots/streaks though appeared comparable to those of pigs of advancing age and cattle were less extensive in goats having the localization of fat in the superficial part of the thickened intima. The intimal elevation also had resemblance to such lesions in pigs. The presence of fibrous plaque was seen mainly in the thoracic aorta featuring small amount of fatty material in the superficial part and calcified foci at the base of the plaque. The relationship of intimal elevation, intimal corrugation, and fibrous plaque with regard to the morphogenesis has been discussed.     

Remodelling of guinea-pig aorta during pregnancy: selective alteration of endothelial cells

It is known that aortic blood flow is increased during pregnancy, which may be due to a pregnancy-associated decrease in aorta sensitivity to vasoconstrictors on one side, and increased response to vasodilators on the other. Recent studies have shown that alteration of blood flow or pressure could remodel some arteries over a short time frame. However, the possibility of remodelling of aorta during pregnancy has not yet been examined. Therefore, the aim of the present study was to assess the morphometric and stereological characteristics of guinea-pig aorta during different stages of pregnancy (non-pregnant, early-pregnant, mid- pregnant, late-pregnant, n = 8-10 for each group). The cross-sectional areas of different aortic layers and of endothelial cells were measured using both light and electron microscopy. The values of external and internal diameters, wall thickness, total cross-sectional area and cross-sectional area of media and adventitia were not significantly different, regardless of the stage of pregnancy. In contrast, the cross- sectional area of intima significantly and progressively decreased during pregnancy (non-pregnant: 61 +/- 5 x 10(4) microm2, late- pregnant: 38 +/- 3 microm2, P < 0.01). The volume:surface density ratio of intima also significantly and progressively decreased during pregnancy (non-pregnant: 5.31 +/- 0.51, late-pregnant: 4.38 +/- 0.42, P < 0.01). Electron microscopy revealed that the cross-sectional area of endothelial cells was significantly decreased during different stages of pregnancy (non-pregnant: 56.8 +/- 6.2 microm2, late-pregnant: 28.9 +/- 3.8 microm2, P < 0.01). It is concluded that during pregnancy there is selective thinning of intimal layer of guinea-pig aorta, which probably reflects hypotrophy of aortic endothelial cells.