Exercise training enhances elastin, fibrillin and nitric oxide in the aorta wall of spontaneously hypertensive rats

This work aimed to analyze the effect of low-intensity exercise training on ultrastructural and molecular aortic remodeling. Male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were allocated into four groups: sedentary WKY (SED-WKY), exercised WKY (EX-WKY, 1 h/day, 5 days/week treadmill exercise training), sedentary SHR (SED-SHR), and exercised SHR (EX-SHR). EX-SHR showed blood pressure reduction of 26% in comparison to SED-SHR after 1 month of exercise (P < 0.05). At the 20th week, BP level was not different between EX-SHRs and WKYs. Circumferential wall tension (CWT) was higher by 77% in SED-SHRs than in SED-WKYs (P < 0.001). Exercise training reduced CWT by 30% in EX- vs. SED-SHR (P < 0.001). In SED-SHRs, endothelial cells showed large and numerous cytoplasmatic vacuoles, fragmented inner elastic lamina and scarce elastin and fibrillin, while exercise training ameliorated it in EX-SHR group. The highest eNOS immunodensity was observed in EX-SHR, which was 50% higher than EX-WKY (P < 0.01) and 120% higher than SED-SHR (P < 0.0001). In conclusion, present findings indicate beneficial effects of exercise training in hypertensive rats since it increased elastin, fibrillin and eNOS content in the aortic wall.     

Biochemical and mechanical behavior of ostrich pericardium as a new biomaterial

We have performed a comparative analysis of glutaraldehyde-preserved ostrich pericardium, as a novel biomaterial, with bovine pericardium. The biochemical characteristics (histology, water content, amino acid composition, and collagen and elastin contents), mechanical properties, and in vivo calcification in a subcutaneous rat model were examined. Ostrich pericardium is slightly thinner and shows a higher water content (70+/-2% vs. 62+/-2%) than bovine pericardium. Additionally, ostrich pericardium presents 1.6-fold lower elastin content and a lower percentage of collagen in reference to the total protein content (68+/-2% vs. 76+/-2%). However, ostrich pericardium shows better mechanical properties, with higher tensile stress at rupture (32.4+/-7.5 vs. 11.5+/-4.6) than calf pericardium. In vivo calcification studies in a rat subcutaneous model show that ostrich pericardium is significantly less calcified than bovine pericardium (23.95+/-13.30 vs. 100.10+/-37.36 mg/g tissue) after 60 days of implantation. In conclusion, glutaraldehyde-stabilized ostrich pericardium tissue shows better mechanical properties than calf tissue. However, calcium accumulation in implanted ostrich tissue is still too high to consider it a much better alternative to bovine pericardium, and anticalcification treatments should be considered.     

Mechanical Behavior of Vessel Wall: A Comparative Study of Aorta,Vena Cava,and Carotid Artery

We have used incremental stress-strain curves to study the mechanical behavior of porcine aorta, carotid artery, and vena cava. Elastic and viscous stress-strain curves are composed of low and high strain regions that are approximately linear. Analysis of the low strain behavior is consistent with previous studies that suggest that the behavior is dominated by the behavior of elastic fibers, and that the collagen and elastic fibers are in parallel networks. At high strain, the behavior is different than that of skin where it is dominated by the behavior of the collagen fibers. The high strain behavior is consistent with a series arrangement of the collagen and smooth muscle; however, the arrangement of smooth muscle and collagen may be different in aorta than in the other vessels studied. It is concluded that the mechanical behavior of the vessel wall differs from the behavior of other extracellular matrices that do not contain smooth muscle. Our results indicate that at least some of the collagen fibrils in the media are in series with smooth muscle cells and this collagen-smooth muscle network is in parallel with parallel networks of collagen and elastic tissue in aorta, carotid artery, and vena cava. It is concluded that the series arrangement of collagen and smooth muscle may be important in mechanochemical transduction in vessel walls and that the exact quantity and arrangement of these components may differ in different vessels. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8715La, 8719Uv, 8719Ff     

Familial co-segregation of the elastin phenotype in skin fibroblasts from Hutchinson-Gilford progeria

Elastin and type IV collagen production are markedly elevated in fibroblasts derived from the skin of patients with Hutchinson-Gilford progeria (HGP). Fibroblasts from three affected children and their parents were compared to normal human skin fibroblasts with respect to elastin production as a function of different concentrations of calf serum and the cytokines, transforming growth factor-beta and basic fibroblast growth factor (TGF-β1, bFGF). In cultured fibroblasts from the parents of probands that were very high elastin producers ( > 10⁵ molecular equivalents/cell per h), at least one parent (mother) presented the same phenotype. Overproduction of elastin in culture could have been due to increased sensitivity of HGP strains to stimuli present in serum; however, relative stimulation of elastin production by calf serum in cell strains from HGP elastin over-producers was less than half the control strain. In most of the culture examined, the responsiveness of elastin production to TGF-β1 was almost absent when compared to the response of normal fibroblasts. HGP strains with high elastin production modified conditioned medium to enhance elastin production in normal cells. These results suggest the presence, in HGP skin fibroblasts, of inheritance of high elastin production that is associated with accelerated aging.     

大鼠心肌细胞和心肌细胞系H9C2表达弹性蛋白

目的 检测弹性蛋白在大鼠心肌细胞和H9C2心肌细胞系内的表达。 方法 取新生和成年SD大鼠各5例的新鲜心脏，冷冻切片；取20只新生3 d SD大鼠心脏，通过0.05%胰蛋白酶和0.075%Ⅱ型胶原酶消化法，获取原代心肌细胞；免疫组织化学和免疫荧光技术检测大鼠心肌组织、原代心肌细胞和H9C2心肌细胞系的弹性蛋白表达;ELISA法检测培养的H9C2心肌细胞系上清中的弹性蛋白。 结果 在大鼠心肌细胞、H9C2心肌细胞系和新生、成年大鼠心肌组织上均发现心肌肌钙蛋白T和弹性蛋白的共表达。免疫组织化学结果发现，弹性蛋白在成纤维细胞、平滑肌细胞和细胞间质内均有表达。H9C2心肌细胞培养液的上清中检测到少量的弹性蛋白。 结论 大鼠心肌细胞表达弹性蛋白，可能参与心肌细胞的势能和细胞间质弹性纤维的构建。     

Effects of physical exercise on the elasticity and elastic components of the rat aorta

Summary To evaluate the effects of exercise on aortic wall elasticity and elastic components, young male rats underwent various exercise regimes for 16 weeks. In the exercised rats, the aortic incremental elastic modulus decreased significantly when under physiological strain. The aortic content of elastin increased significantly and the calcium content of elastin decreased significantly in the exercised group. The accumulated data from the exercised and sedentary groups revealed that the elastin calcium content was related positively to the incremental elastic modulus. We concluded that physical exercise from an early age decreases the calcium deposit in aortic wall elastin and that this effect probably produced in the exercised rats a distensible aorta.     

Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms

Interstitial deletion of 7q11.23–q21.11 was identified by cytogenetic methods in a 4-year-old boy with Williams syndrome (WS) and infantile spasms. Deletion of the elastin (ELN) gene and the DNA polymorphic markers, D7S1870, D7S2490, D7S2518, and D7S2421, were identified in the patient, but the loci for D7S653 and D7S675 were not involved. Zackowski et al. (1990) reported that 6 of 16 patients with the interstitial deletion of 7q11.2–q22 had abnormal electro encephalograms, or seizures, or both, and that infantile spasms were present in 2 of the 6 patients. WS is a well defined developmental disorder characterized by distinct facial features, gregarious personality, and congenital heart defects. Seizures are not generally associated with this syndrome. WS commonly is characterized by deletion of the loci for ELN and D7S1870, but not those for D7S2490, D7S2518, or D7S2421. This suggests that a gene responsible for infantile spasms is located in the 2.7-cM interval between loci D7S1870 and D7S675. Received: April 27, 1998 / Accepted: May 29, 1998     

Annulo-aortic ectasia

Summary The aortic wall of the human ascending aorta from 44 patients operated on for annulo-aortic ectasia (AAE) was studied. Light microscopy revealed significantly greater cystic change, elastic fragmentation, fibrosis and disappearance of smooth muscle cells in aortic media in AAE than in control specimens taken at autopsy. Occasional aortae, however, were morphologically almost normal. Eight of the patients had Marfan's syndrome. No significant differences were observed between them and the other 36 patients, except for a tendency to have less pronounced fibrosis. There were 9 patients who, in addition to the changes mentioned, had advanced atherosclerosis, and their aortae showed more extensive fibrosis and medial necrosis. Pooling of proteoglycan matrix, degeneration of elastic lamellae, increased amount of collagen and necrosis of smooth muscle cells characterized the electron microscopic findings of 13 patients. The collagen fibers seemed to be of normal shape. In conclusion, changes in annulo-aortic ectasia are characterized by severe cystic medial necrosis. The changes are basically similar in Marfan and non-Marfan patients.     

Medical overview and genetics of Williams-Beuren syndrome

Williams-Beuren syndrome (WBS) is a multisystem genetic disorder caused by a microdeletion on chromosome 7. The majority of patients demonstrate cardiovascular pathology, most commonly supravalvular aortic and/or other vascular stenoses. Progressive stenosis can occur and, furthermore,  50% of WBS patients develop hypertension. Although the absolute risk for life-threatening cardiovascular complications is low, certain constellations of problems such as severe biventricular outflow disease increase the relative risk of adverse outcomes. Many additional medical problems complicate WBS such as feeding difficulties, colic and irritability, slow physical growth, abnormal dentition, constipation, and a variety of endocrine abnormalities. All patients with WBS have intellectual handicaps. Most patients function in the range of moderate mental retardation and also demonstrate a characteristic cognitive profile of strengths and weaknesses; notably most individuals with WBS develop anxieties and phobias. The typical, albeit subtle, facial dysmorpology of WBS in conjunction with one or more of the above problems should prompt fluorescence in situ hybridization (FISH) laboratory testing to confirm deletion of one copy of the elastin gene. Almost all WBS patients have the same size microdeletion on one chromosome 7 resulting in loss of one copy of  20 genes. The role these genes play in causing the complex WBS phenotype is actively being studied in several research laboratories. Patients with WBS require long-term care and guidelines for medical management and anticipatory guidance are offered.     

Failure properties of ascending thoracic aortic aneurysms with dysfunctional tricuspid aortic valves

 Open in a separate windowOBJECTIVESAscending thoracic aortic aneurysms (ATAAs) often coexist with dysfunctional tricuspid aortic valves (TAVs). How valvular pathology relates to the aortic wall mechanical properties requires detailed examination.METHODSIntact-wall and layer-specific mechanical properties from 40 and 21 patients with TAV-ATAAs, respectively, were studied using uniaxial tensile testing, longitudinally and circumferentially. Failure stress (tensile strength), failure stretch (extensibility) and peak elastic modulus (stiffness) measurements, along with histological assays of thickness and elastin/collagen contents, were compared among patients with no valvular pathology (NVP), aortic stenosis (AS) or aortic insufficiency (AI).RESULTSIntact-wall stiffness longitudinally and medial strength and stiffness, in either direction, were significantly lower in AI patients than in AS and NVP patients. Intact-wall/medial thickness and extensibility in either direction were significantly lower in AS patients than in AI and NVP patients. In contrast, intact-wall/medial stiffness circumferentially was significantly higher in AS patients than in NVP patients, consistent with the significantly increased medial collagen in AS patients. Failure properties and medial thickness and elastin/collagen contents were significantly lower (more impaired) in females. The left lateral was the thickest quadrant in NVP patients, but the 4 quadrants were equally thick in AS and AI patients. There were significant differences in strength and stiffness among quadrants, which varied however in the 3 patient groups.CONCLUSIONSThe aortic wall load-bearing capacity was impaired in patients with ATAA in the presence of TAV stenosis or insufficiency. These findings lend biomechanical support to the current guidelines suggesting lower thresholds for elective ascending aorta replacement in cases of aortic valve surgery.