Neonatal intima formation in the human coronary artery.

Intimal masses develop in the human coronary arteries of all humans, becoming atherosclerotic in later life either because of focal accumulation of lipid or the resulting response to injury. We evaluated the time course of formation of the intimal mass in the proximal left anterior descending coronary artery in autopsy specimens from 91 patients between 17 weeks' gestation and 23 months of postnatal age. Intima was rarely found before 30 weeks' gestation; however, the frequency with which at least some intimal cells were observed increased to 35% between 36 weeks' gestation and birth. By 3 months after birth, all patients had an intimal mass at this coronary location. The mean intima/media ratio was 0.1 just after birth and increased continuously to the second postnatal year. Replication of medial smooth muscle cells, indicated by proliferating cell nuclear antigen staining, was high before birth and decreased between birth and 2 years of age. However, the replication index of the intima remained at 2% to 5%. Thus, coronary intimal cells appearing in the perinatal period may arise by migration after replication of medial smooth muscle, as is seen in models of carotid artery balloon injury. In conclusion, formation of the coronary artery intima is a rapid process, beginning in the peripartum or postpartum period. Given the clonality of the adult lesion and the lack of proliferation in later stages of lesion formation, it is intriguing to speculate that this event may form the basis for atherosclerosis in later life.     

Evidence concerning resistance to atheroma by media-like islands in the intima of coronary arteries

Coronary arteries with and without atheroma are compared histologically to ask what kind of artery encourages atheroma. When atheroma obliterates the structures that preceded and invited its intrusion, the sites remaining for observation form a censored data set. How to assess media-like island effects using the censored data set is the objective here. Full length of right coronary artery is prepared for H&E-stained paraffin sections. At sites lacking atheroma, measurements are taken for intimal thickness (FT), SMC numbers (CT), and their ratio, fibroplastic thickness per SMC, FC = FT/CT. Arteries with atheroma tend to have greater values for all three variables, FC, FT, and CT. Mathematical models compensating for data set censoring imply that atheroma selectively favors sites with much fibroplasia and few SMCs, i.e. high FC. Frequently encountered media-like islands in the coronary intima showed ambiguous evidence of weakly repelling atheroma. Fibroplastic intimal thickening measured by FC progresses relentlessly with age. The sites with the greatest fibroplasia seem to be the most prone to selective obliteration by atheroma. Media-like islands seem to protect only the local sites and not the whole artery from atheroma.     

经皮穿刺旋磨动脉内膜促动脉自闭动物实验

目的为应用新方法治疗动脉导管未闭(PDA)提供实验数据和间接证据。方法 11条实验犬,犬龄为14～20个月,(16.7±3.2)个月,体重为20～25kg,(22.7±2.5)kg。经皮穿刺左右腋动脉造影,测量腋动脉内径3.2～4.8mm,(3.9±0.6)mm,选择合适型号旋磨器(在测量动脉直径基础上增加1.0～1.5mm,作为选择旋磨器的标准),旋磨腋动脉内膜,旋磨术后4周再次行腋动脉造影,观察腋动脉内径变化,最后处死实验犬,取左右腋动脉行病理检查。结果旋磨22条腋动脉均有不同程度变化,其中8条动脉完全闭合,12条动脉内径不同程度狭窄,其中4条动脉比旋磨术前狭窄≥2/3,4条动脉比旋磨术前狭窄1/2,4条动脉比旋磨术前狭窄1/3,闭合率为36.4%,总有效率为90.9%。另外2条动脉比旋磨术前狭窄<1/3,视为无效。结论经皮穿刺旋磨动脉内膜,可促动脉自闭,为应用新方法治疗PDA提供了实验数据和间接证据。     

Endothelial Gi protein in human coronary arteries

Endothelium-dependent relaxations mediated by Gi protein areprominently impaired in atherosclerotic coronary arteries. However,it remains to be determined whether the expression of endothelialGi protein per se is reduced in coronary atherosclerosis. Thus,in the present study the expression of endothelial Gi proteinwas examined by immunohistochemical staining using a specificantibody against human Gi protein (-subunits of G_1–1 andG_1–2 proteins) in the proximal segment of the left anteriordescending coronary arteries (segment 6) from 40 consecutiveautopsy cases. The immunoreactive level of the Gi protein wassemi-quantitated in four grades (none, 0; slight, +; moderate,+2; high, +3) and the mean value of the ratings of all endothelialcells was used as an index of the endothelial Gi protein expressionof the artery. The immunoreactive level of the Gi protein inhuman coronary arteries was significantly reduced with ageingand extent of coronary atherosclerosis (both P<0.05), andwas lower in patients with than in those without hypertension(P<0.01) or hyperlipidaemia (P<0.05). In addition, thelevel was significantly lower in the eccentric portions thanin the concentric ones in each atherosclerotic coronary artery(P<0.0001). These alterations in the immunoreactive levelof endothelial Gi protein in human coronary arteries may explain,in part, why Gi protein-mediated, endothelium-dependent relaxationsare prominently impaired in atherosclerosis.     

Cell proliferation in human coronary arteries.

Despite the lack of direct evidence for cell multiplication, proliferation of smooth muscle cells in human atherosclerotic lesions has been assumed to play a central role in ontogeny of the plaque. We used antibodies to cell cycle-related proteins on tissue sections of human arteries and coronary atherosclerotic plaques. Specific cell types were identified by immunochemical reagents for smooth muscle, monocyte-macrophages, and other blood cells. Low rates of smooth muscle cell proliferation were observed. Macrophages were also observed with rates of proliferation comparable to that of the smooth muscle. Additional replicating cells could not be defined as belonging to specific cell types with the reagents used in this study. These findings imply that smooth muscle replication in advanced plaques is indolent and raise the possibility of a role for proliferating leukocytes.     

The heart of coronary arteries

A 67-year-old man with a medical history notable for treatedtype II diabetes, dyslipidaemia and hypertension, was admittedto the hospital     

The intima media thickness and coronary risk factors.

BACKGROUND: AIM: to estimate the degree of atherosclerosis in the carotids with different measurements of the intima media thickness (IMT), obtained by ultrasound and to analyze the correlations of these measures to coronary risk factors. METHODS: DESIGN AND PARTICIPANTS: 130 employed men and women volunteered after public announcement. MEASURES: Health and life-style were charted using a comprehensive questionnaire. Anthropometric measurements, and blood pressure after 10 min of rest were obtained at clinical examination. Blood tests included analyses for fibrinogen, cholesterol, and HDL-cholesterol. The IMT was measured bilaterally three times at the transition of a. carotis to bulbus as well as on a. carotis 0.5 cm proximal thereto. Analyses were conducted with four methodologically different ways of expressing IMT as the dependent variable: IMT(left), IMT(communis), IMT(mean) and IMT(max). RESULTS: Among the measurements of IMT, IMT(max) showed the strongest correlations to coronary risk factors, significantly associated with sex and age. In univariate analyses only the degree of physical activity in the leisure time correlated significantly to IMT(max) among men. When adjusted for age, HDL-cholesterol, BMI, systolic blood pressure and physical activity in leisure time in a multiple linear regression analysis IMT(max) showed significant correlations to physical activity in leisure time and systolic blood pressure among men older than 45 years. Among women IMT(max) was significantly correlated to HDL-cholesterol (inversely), which remained significant in the multiple regression analysis including the same factors as for men. CONCLUSIONS: IMT(max) among four measures of IMT showed the strongest associations to coronary risk factors in otherwise healthy individuals.     

Mechanism of histamine actions in human coronary arteries

Helical strips of human coronary arteries contracted in response to histamine concentration dependently, they relaxed with low concentrations and contracted with high concentrations. Treatment with cimetidine potentiated contraction in the strips with intact and damaged endothelium to a similar extent and attenuated relaxation. Removal of endothelium abolished relaxation and potentiated contraction in the cimetidine-treated strips. Methylene blue increased the contractile response to histamine in the strips with endothelium but did not alter the response in the damaged-endothelium strips. Histamine-induced relaxations in the intact strips were suppressed or abolished by treatment with ETYA, AA861, a lipoxygenase inhibitor, and by chlorpheniramine but were unaffected by indomethacin. Chlorpheniramine also abolished amine-induced contraction. It may be concluded that histamine-induced contraction in human coronary arteries is mediated by H1 receptors in smooth muscle, and relaxation is mediated by H2 receptors in smooth muscle and H1 receptors in endothelium. Also, stimulation of the endothelial H1 receptor liberates vasodilator substance and possibly activates smooth muscle guanylate cyclase to accumulate cellular cyclic guanosine monophosphate.     

Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries

OBJECTIVES: Reduced nitric oxide (NO) bioavailability is a key mechanism in the development of endothelial dysfunction. The NO synthase cofactor, tetrahydrobiopterin (BH4), increases NO availability, yet its effect in the human coronary circulation, particularly following PCI, remains uncertain. This study was designed to evaluate the effects of intracoronary BH4 in human coronary arteries with non-critical coronary artery disease or following percutaneous coronary intervention (PCI). METHODS: The study group consisted of 57 stable patients, 10 of which were controls. Active drug was administered in 47 patients, with either de novo non-critical coronary disease (non-stent group; n=25) or following PCI (stent group; n=22). Coronary blood flow (CBF) was measured (0.014-inch Doppler flow wire) in each of these groups in response to sequential intracoronary infusions of acetylcholine (Ach, 10(-7) & 10(-6) M), BH4 (250 mug/min & 500 mug/min) and a co-infusion of BH4 (500 mug/min) and Ach (10(-7) & 10(-6) M). The primary endpoint evaluated the % change in CBF to Ach compared to co-infusion of Ach and BH4. RESULTS: Mean age was 60+/-10 years (M 45:F 12). Regarding the primary hypothesis, no difference was observed between Ach response compared to co-infusion of BH4 and Ach in the % change in CBF in either the non-stent group (Ach 97+/-122%, Ach/BH4 87+/-95%) or the stent group (Ach 77+/-105%, Ach/BH4 55+/-97%). CONCLUSIONS: In native non-critical coronary artery disease or following PCI, coronary microvascular endothelial function is not improved by co-administration of Ach and BH4.     

Fibronectin content of the intima of normal and atherosclerotic arteries

An immunofluorescent study demonstrated the localization of fibronectin and collagen of types 1, 3, 4 and 5 in normal arterial intima and atherosclerotic patches. In the atherosclerotic patches, fibronectin is mostly grouped among cells of smooth-muscle origin together with collagen of type 4, while the fibrous tissue of the patches contains little fibronectin. It is assumed that changed extracellular matrix composition reflects the development of atherosclerotic patches, and fibronectin can be regarded as a marker of early stages of atherosclerosis.