Figure 2. Comparative structure and injury responses of the arterial versus capillary vasculatures under healthy and disease states.

A single layer of endothelial cells (ECs) lines the entire vascular system, while the ECM is the major constituent of the vessel wall, particularly in larger vessels. Arteries and arterioles both have three ECM layers: tunica intima (a single layer of ECs attached to the subendothelial layer and internal elastic lamina), tunica media (circumferential layers of vascular smooth muscle cells and elastic lamellae with interspersed basement membrane and interstitial matrix components), and tunica adventitia (separated from tunica media by external elastic lamina and contains fibroblasts, progenitor cells, immune cells, and a capillary vasculature embedded in interstitial collagenous matrices). On the contrary, capillaries consist only of a single layer of ECs, a thin sheet of basement membrane, and surrounding pericytes. Compared to arteries and arterioles, capillaries have the least amount of matrix crosslinking and mural cell cellularity, which is represented by smooth muscle in arteries/arterioles, and pericytes in capillaries. Because of the structural and ECM differences between arteries/arterioles compared to capillaries, the two vessel groups react in a markedly distinct manner when exposed to injurious stimuli. ECM remodeling in response to injury occurs mostly in arteries and least in capillaries. Under disease states, capillaries are most prone to vascular regression due to inherently less interstitial collagen matrices (and a lack of an elastin-rich matrix), fewer mural cells, and reduced matrix cross-linking compared to arteries and arterioles. During injury responses, arteries and arterioles undergo matrix degradation (including degradation of elastic lamellae, interstitial collagens, and basement membrane), physical and functional cell loss with SMC dedifferentiation events, reactive ECM remodeling that includes provisional matrix deposition, exposure of previously hidden matricryptic integrin binding sites, and synthesis of new injury-induced ECM components as well as interstitial collagens and proteoglycans (i.e. vessel fibrosis response); and intimal hyperplasia of activated SMCs as well as other cell types which accumulate from the circulation or the adventitia. Key growth factors, such as TGFβ isoforms, and proinflammatory mediators such as IL-1β, TNFα and thrombin are liberated during these injuries to regulate these processes. These adverse changes in arteries and arterioles lead to mostly chronic disease states (the larger more stable vessels persist) including atherosclerosis, hypertension, aneurysms (microaneurysms in very small arteries and arterioles), and vasculitis. In contrast, capillaries readily undergo inflammatory mediator-induced tube regression with EC loss and accompanying degradation of the basement membrane. A spectrum of responses occurs downstream of capillary regression including increased vascular permeability, tissue hemorrhage, and parenchymal cell dysfunction or loss due to ischemia, lack of nutrients, or reduced removal of waste products. EC: endothelial cell, ECM: extracellular matrix, BM: basement membrane, SM: smooth muscle cell.