Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.
Arterioscler Thromb Vasc Biol
; 43(9): 1599-1616, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37409533
ABSTRACT
Because of structural and cellular differences (ie, degrees of matrix abundance and cross-linking, mural cell density, and adventitia), large and medium-sized vessels, in comparison to capillaries, react in a unique manner to stimuli that induce vascular disease. A stereotypical vascular injury response is ECM (extracellular matrix) remodeling that occurs particularly in larger vessels in response to injurious stimuli, such as elevated angiotensin II, hyperlipidemia, hyperglycemia, genetic deficiencies, inflammatory cell infiltration, or exposure to proinflammatory mediators. Even with substantial and prolonged vascular damage, large- and medium-sized arteries, persist, but become modified by (1) changes in vascular wall cellularity; (2) modifications in the differentiation status of endothelial cells, vascular smooth muscle cells, or adventitial stem cells (each can become activated); (3) infiltration of the vascular wall by various leukocyte types; (4) increased exposure to critical growth factors and proinflammatory mediators; and (5) marked changes in the vascular ECM, that remodels from a homeostatic, prodifferentiation ECM environment to matrices that instead promote tissue reparative responses. This latter ECM presents previously hidden matricryptic sites that bind integrins to signal vascular cells and infiltrating leukocytes (in coordination with other mediators) to proliferate, invade, secrete ECM-degrading proteinases, and deposit injury-induced matrices (predisposing to vessel wall fibrosis). In contrast, in response to similar stimuli, capillaries can undergo regression responses (rarefaction). In summary, we have described the molecular events controlling ECM remodeling in major vascular diseases as well as the differential responses of arteries versus capillaries to key mediators inducing vascular injury.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Vasculares
/
Lesões do Sistema Vascular
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article