Review: Vascular remodeling: implications for small artery function and target organ damage

Abstract

At the level of the small artery, essential hypertension is associated with eutrophic inward remodeling. This involves reduction in lumen diameter by an increase in wall thickness. Previously thought to involve either hypertrophy or hyperplasia of the vascular smooth muscle cells in the media, it is now felt to be mediated by a functional property of the wall: myogenic tone. This is the ability of an artery to contract in response to an increase in intraluminal pressure. This autoregulatory function is also vital to ensure stabilisation of distal capillary pressures and so prevent, or limit, organ damage. Indeed in any animal model studied, when myogenic autoregulation is affected, target organ damage ensues. We have also observed, in two studies, that when myogenic autoregulation is damaged in the context of hypertension, eutrophic remodeling is replaced by an outward growth of the arterial wall with preservation of lumen diameter. This is called hypertrophic remodeling and, independently, has been observed by a number of groups in small arteries from patients with type 2 diabetes. We believe that this is a key reason for the unique propensity to hypertensive injury seen in patients with diabetes. We also discuss the significance of integrins, transmembrane proteins with wide ranging functions; from initiation of cell migration to intracellular signalling. Two particular integrins, alpha5beta1 and alphanubeta3, have been found to be necessary for both normal myogenic autoregulation and eutrophic remodeling and the possibility that damage to these may occur in diabetes is examined.

Integrin β3 mediates cerebrovascular remodelling through Src/ClC‐3 volume‐regulated Cl− channel signalling pathway

“…Consistent with our previous studies in 2K2C hypertensive rats (Shi et al, 2007;Liu et al, 2010;Wang et al, 2012), cerebral vessels from Ang II-infused hypertensive mice in the present study underwent the hypertrophic remodelling process, which is characterized by increases in blood vessel wall thickness, outer blood vessel wall diameter, CSA and a reduction in inner blood vessel wall diameter Shi et al, 2007;Liu et al, 2010). This is different from he αv-mediated eutrophic remodelling, which is characterized by a reduction in lumen diameter and unchanged CSA (Sonoyama et al, 2007). The signs of vascular remodelling are not uniform across vessel types or animal models, for example, pial arteries with smaller lumens and thicker walls were found in SHRSP (Chillon et al, 1996), L-NAME-induced hypertensive rats (Kitamoto et al, 2000), DOCA-salt hypertensive mice (Liu et al, 2010;Zheng et al, 2013); however, in 1-kindey 1-clip hypertensive rats, pial arterioles displayed thicker walls but normal lumens (Baumbach and Hajdu, 1993).…”

Small Artery Remodeling: Current Concepts and Questions

“…increased diameter at increased pressure) and hypertrophic responses to hypertension. In support of this view, in hypertensive models with compromised myogenic responses, small vessels show hypertrophic remodeling [165]. …”

Arterial Function in Cardio-Metabolic Diseases: From the Microcirculation to the Large Conduits

“…When the myogenic response is intact, eutrophic inward remodeling is the main response to changes in pressure, whereas in a dysfunctional system i.e., when the changes in pressure overwhelms myogenic autoregulation, then hypertrophic remodeling occurs. 37 …”