Role of the extracellular matrix in age-related modifications of the rat aorta. Ultrastructural, morphometric, and enzymatic evaluations.

Abstract

Connective tissues such as blood vessels are known to be greatly affected by age because of impaired functional properties and increased susceptibility to diseases. With the aim of providing further information on the role of the extracellular matrix in age-related modifications, we investigated the aorta in the rat model from birth to senescence by means of morphological and morphometric observations and by evaluation of lysyl oxidase activity. Results focused on the dramatic vascular rearrangements due to progressive fibrosis of the extracellular matrix and on prominent elastin modifications. The presence of lysyl oxidase activity, even in the oldest animals, might be at least partly responsible for the increased stiffness of the aging extracellular matrix. The striking age-related remodeling of the aortic architecture and the alterations of the interactions between cellular and extracellular compartments might greatly influence the functional properties of the arterial wall in senescence, at least contributing to the consequences of some apparently age-related vascular disorders. ( integrated system composed of collagen fibrils, elastic lamellae, proteoglycans, minor collagens, and structural glycoproteins that, together with cells, guarantees the major properties of the vascular compartment, i.e., the diffusion at proper rates of nutrients and other metabolic factors through optimal blood flow. -4Apart from calcifications, fibrosis, and atheromatous lesions, which are frequently observed in the vessel wall of several species 5 " 9 and which are at least partly responsible for the failure of the cardiovascular system with age, 7 little is known about the pathogenesis of the age-related modifications of the vessel wall, which may affect vascular properties such as elasticity and resilience and which may be of paramount importance in understanding specific pathological conditions. The present work was undertaken with the aim of focusing attention on the age-related modifications of the aortic arch in rats from birth to senescence. Qualitative and quantitative morphological data concerning the structure and distribution of the cellular and extracellular components were correlated with the activity of lysyl oxidase, the enzyme that catalyzes the formation of collagen and elastin cross-links and therefore contributes to the stabilization of these two polymers. Supported by Fondi (40%) and Ministero Universita e Ricerca Scientifica e Technologica (60%).Address for correspondence: Prof. C. Fornieri, 1st. Patologia Generale, Via Campi 287, 41100 Modena, Italy.Received April 21, 1992; accepted May 13, 1992. In the light of our results, we suggest that the interactions of the cellular and the extracellular compartments and the ratio between collagen and elastin play key roles in conditioning the morphological-functional properties of the arterial wall and, therefore, explain at least some of the consequences (although not the pathogenesis) of several pathological processes affecting the vascular compartment with inc...

Accumulation of Advanced Glycation Endproducts in the Rat Nephron: Link with Circulating AGEs During Aging

“…There are two types of collagen crosslinking: crosslinks mediated by lysyl oxidase and those derived from glycation. The decrease in lysyl oxidase-mediated crosslinks in interstitial collagen is in agreement with the finding that lysyl oxidase activity decreases with age (Sanada et al 1978;Fornieri et al 1992). These data suggest that the AGEmediated collagen crosslinks indicated by increased collagen fluorescence in our study are the main cause of the structural alteration in GBM that occurs with aging.…”

Relaxin Therapy Reverses Large Artery Remodeling and Improves Arterial Compliance in Senescent Spontaneously Hypertensive Rats

“…High blood pressure exacerbates the situation by forcing the artery to work in a less compliant range. 32,34,35 We found that, unlike the curly shaped elastin fibers in aortas from aged WKY rats, elastin fibers in the aorta of SHRs were straight and remained unchanged after relaxin therapy. Relaxin therapy significantly reduced collagen content, estimated either as total content per centimeter segment or percentage of dry weight but without change in elastin level, resulting in a significant increase in the elastin:collagen ratio and arterial compliance.…”

“…Previous studies revealed that arterial collagen content increased progressively with aging and became more insoluble and crosslinked. 30,32 In sharp contrast, vascular elastin synthesis is active in newborn and young rats, and becomes quiescent in aged animals resulting a reduced elastin:collagen ratio. 33 Elastin is more extensible, but collagen fibers are very rigid.…”

Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function

“…4 -6 Studies from our laboratory and others have shown that diffuse intimal thickening with aging is characterized by accumulation of fibronectin, collagen, and vascular smooth muscle cells (VSMCs), with an increase in matrix metalloproteinase (MMP)-2 and angiotensin II (Ang II) expression. [7][8][9][10][11] In addition, the expression of aortic intracellular adhesion molecule and transforming growth factor-␤1 markedly increases with age, and these molecules localize to MMP-2-staining positive areas. 12 Arterial aging is also characterized by an increase in NAD(P)H oxidase activity and reactive oxygen species production and a reduction in nitric oxide (NO) bioavailability.…”