Elastolytic and Collagenolytic Studies of Arteries

Dobrin, Philip B.; Baker, William H.; Gley, W. C.

doi:10.1001/archsurg.1984.01390160041009

Cited by 357 publications

(67 citation statements)

References 15 publications

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“…6 Were fragmentation of the medial elastic network to occur in this Marfan model, then the aortic wall would stiffen, as previously reported in studies evaluating the impact of elastases 7 or elastocalcinosis. 8 A loss of aortic wall elasticity would lead to increased cyclic stress and pulse pressure, thereby amplifying aortic dilatation.…”

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confidence: 60%

Aortic Wall Mechanics and Composition in a Transgenic Mouse Model of Marfan Syndrome

Marque

Kieffer

Gayraud

et al. 2001

ATVB

112

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Abstract-In Marfan syndrome, mutations of the fibrillin gene (FBN1) lead to aneurysm of the thoracic aorta, making the aortic wall more susceptible to dissection, but the precise sequence of events underlying aneurysm formation is unknown. We used a rodent model of Marfan syndrome, the mgR/mgR mouse (with mgR: hypomorphic FBN1 mutation), which underexpresses FBN1, to distinguish between a defect in the early formation of elastic fibers and the later disruption of elastic fibers. The content of desmosine plus isodesmosine was used as an index of early elastogenesis; disruption of elastic fibers was analyzed by histomorphometry. Because disruption of the medial elastic fibers may produce aortic stiffening, so amplifying the aneurysmal process, we measured thoracoabdominal pulse wave velocity as an indicator of aortic wall stiffness. Both mgR/mgR and wild-type (C57BL/6J-129SV) strains were normotensive, and wall stress was not significantly modified because the increase in internal diameter (0.80Ϯ0.06 vs 0.63Ϯ0.03 mm in wild type, PϽ0.05) was accompanied by increased medial cross-sectional area. The aortic wall stiffened (4-fold increase in the elastic modulus-to-wall stress ratio). Desmosine content was not modified (mgR/mgR 432Ϯ31 vs wild type 492Ϯ42 g/mg wet weight, PϾ0.05). Elastic fibers showed severe fragmentation: the percentage of the media occupied by elastic fibers was 18Ϯ3% in mgR/mgR mice vs 30Ϯ1% in wild-type mice, with the number of elastic segments being 1.9Ϯ0.2 vs 1.4Ϯ0.1ϫ10 Ϫ6/mm 2 in the wild type (both PϽ0.05). In conclusion, underexpression of FBN1 in mice leads to severe elastic network fragmentation but no change in cross-linking, together with aortic dilatation. This result suggests that fragmentation of the medial elastic network and not a defect in early elastogenesis is 1 of the determinants of aortic dilatation in Marfan syndrome. Key Words: fibrillin-1 Ⅲ elastic modulus Ⅲ aneurysm Ⅲ desmosines Ⅲ elastic fibers M arfan syndrome is a dominantly inherited disorder characterized by cardiovascular, skeletal, and ocular abnormalities. 1 The cardiovascular manifestations include aortic root dilatation and dissection that result in rupture of the vessel wall and premature death. Marfan syndrome has been associated with mutations of the gene coding for fibrillin-1 (FBN1), the major constituent of extracellular microfibrils. 2 However, the link between FBN1 deficiency and the development of aneurysm is not yet clearly established.Early ideas were based on the regulatory role played by microfibrils in the organized deposition of tropoelastin molecules during elastogenesis. 3 It was suggested that FBN1 mutations prevented normal cross-linking (formation of desmosine cross-bridges), leading to disorganized microfibrillar assembly, and that this weakened the mechanical strength of the media. This hypothesis was recently challenged by homologous gene-targeting experiments in the mouse, 4 which indicated that FBN1 microfibrils were predominantly engaged in global tissue homeostasis rather than in elasti...

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confidence: 60%

Aortic Wall Mechanics and Composition in a Transgenic Mouse Model of Marfan Syndrome

Marque

Kieffer

Gayraud

et al. 2001

ATVB

112

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“…In normal small arterioles, the adventitial inner part contains elastic fibers. It has been suggested that circumferential arterial wall stress may be borne primarily by elastin (8). The high expression of MMP-2 and MMP-9 in the adventitia suggests an active role in degradation of elastin and other extracellular matrix components to facilitate enlargement of growing collateral vessels.…”

Section: Discussionmentioning

confidence: 99%

Remodeling of the adventitia during coronary arteriogenesis

Cai

Koltai

Kocsis

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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We studied the role of the adventitia in adaptive arteriogenesis during the phase of active growth of coronary collateral vessels (CV) induced by chronic occlusion of the left circumflex coronary artery in canine hearts. We used electron microscopy and immunoconfocal (IF) labeling for bFGF, matrix metalloproteinase (MMP)-2, MMP-9, tissue-type plasminogen activator (tPA), its inhibitor (PAI-1), fibronectin (FN), and Ki-67. Proliferation of smooth muscle cells and adventitial fibroblasts was evident. Quantitative IF showed that adventitial MMP-2, MMP-9, and FN were 9.2-, 7.5-, and 8.6-fold, bFGF was 5.1-fold, and PAI-1 was 3.4-fold higher in CV than in normal vessels (NV). The number of fibroblasts was 5-fold elevated in CV, but the elastic fiber content was 25-fold greater in NV than in CV. Perivascular myocyte damage and induction of endothelial nitric oxide synthase in peri-CV capillaries indicate expansion of CV. It was concluded that adventitial activation is associated with the development of CV through cell proliferation, production of growth factors, and induction of extracellular proteolysis thereby contributing to remodeling during adaptive arteriogenesis. collateral vessel growth; metalloproteinases; extracellular proteolysis; dog CORONARY COLLATERAL VESSEL GROWTH in the dog heart, induced by chronic occlusion of a major coronary artery, results in a 20-50 times increase in diameter (21). The mechanism of collateral vessel growth is only partially understood. Many factors or events have been indicated to make contributions to this process, e.g., increased shear stress, early invasion of monocytes/ macrophages, reexpression of fetal proteins, extracellular proteolysis, migration of smooth muscle (SM) cells, and involvement of gap junction proteins (3,4,29). The notion that apoptosis of SM cells, fibroblasts, or myocytes creates space for the enlargement of collateral vessels has also been proposed (23). These studies addressed the crucial role of endothelium and of SM cells in the development of coronary collateral vessels.However, the importance of the tunica adventitia in vascular remodeling was largely neglected, although enlargement of collateral vessels without participation of the adventitia seems not conceivable. We hypothesize that the adventitia is activated and might be an important contributor to the development of coronary collaterals.The development of coronary collateral vessels has been classified into three phases: early growth (2-3 wk postsurgery), active growth (4-6 wk postsurgery), and maturation (8-12 wk postsurgery) (4). An early study showed that an acute inflammatory reaction was present in the adventitia of collateral vessels in the phase of early growth (2). However, in the phases of active growth and maturation, inflammatory cells have not been observed in the adventitia, and fibroblasts are the predominant cells residing in the adventitia. Fibroblasts have been demonstrated to be active participants in vascular remodeling (20,25,26). Here, we studied the question whether typica...

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“…The abdominal aorta tapers geometrically and has higher blood pressures 28) , and is stiffer with less elastin and more collagen 28) . Vasa vasorum is common in the thoracic aorta but rare in the abdominal aorta 29) . These features may explain the different susceptibilities to risk factors between the aortas.…”

Section: )mentioning

confidence: 99%

Associations Between Plasma C-reactive Protein Levels and the Severities of Coronary and Aortic Atherosclerosis

Momiyama¹,

Ohmori²,

Fayad³

et al. 2010

JAT

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Aim:Limited correlations between C-reactive protein (CRP) and coronary artery disease (CAD) have been reported. Recently, MRI became a useful tool for non-invasively evaluating atherosclerotic plaques in thoracic and abdominal aortas. Methods: To elucidate the associations between plasma CRP levels and the severities of coronary and aortic atherosclerosis, we performed aortic black-blood MRI in 136 patients undergoing coronary angiography. For each patient, 9 slices of thoracic aorta and 9 slices of abdominal aorta were obtained at 12-mm intervals, and the plaque extent in each slice was scored. The degree of aortic atherosclerosis is represented as the sum of scores. The degree of coronary atherosclerosis is represented as the number of 50% stenotic vessels and 25% stenotic segments.

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Elastolytic and Collagenolytic Studies of Arteries

Cited by 357 publications

References 15 publications

Aortic Wall Mechanics and Composition in a Transgenic Mouse Model of Marfan Syndrome

Aortic Wall Mechanics and Composition in a Transgenic Mouse Model of Marfan Syndrome

Remodeling of the adventitia during coronary arteriogenesis

Associations Between Plasma C-reactive Protein Levels and the Severities of Coronary and Aortic Atherosclerosis

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