Pathophysiology of vascular remodeling in hypertension

Abstract

Vascular remodeling refers to alterations in the structure of resistance vessels contributing to elevated systemic vascular resistance in hypertension. We start with some historical aspects, underscoring the importance of Glagov's contribution. We then move to some basic concepts on the biomechanics of blood vessels and explain the definitions proposed by Mulvany for specific forms of remodeling, especially inward eutrophic and inward hypertrophic. The available evidence for the existence of remodeled resistance vessels in hypertension comes next, with relatively more weight given to human, in comparison with animal data. Mechanisms are discussed. The impact of antihypertensive drug treatment on remodeling is described, again with emphasis on human data. Some details are given on the three mechanisms to date which point to remodeling resistance arteries as an independent predictor of cardiovascular risk in hypertensive patients. We terminate by considering the potential role of remodeling in the pathogenesis of endorgan damage and in the perpetuation of hypertension.

Figure 1

Changes are predominantly in media-to-lumen ratio (M/L), changing the vessel wall width for increased muscle mass (Figure 1(A)) or in the reorganization of cellular and noncellular elements (Figure 1(B)). Another mechanism of remodeling mainly involves changes in the dimensions of the lumen (Figures 1(C) and 1(D)). In this case, the restructuring of the active components and cell signals does not result in significant changes in the dimensions of the vascular lumen. Another form of vascular remodeling is microcirculation rarefaction (Figures 1(E) and 1(F)).

Figure 2

Schematic representation for the adaptation of these changes in different pathologies, including structural changes to the intima layer that contribute to remodeling of the vascular wall. Thus, outward remodeling compensates for atherosclerotic plaque growth and delays the progression of blood flow limitation during stenosis, whereas during restenosis, intimal hyperplasia causes a narrowing of the lumen.

Figure 3

Associated intracellular cascades to physiopathology of vascular remodeling. In FFHR experimental model, the route associated with the satellite receptor and the IGFR subunit associated with NAD(P)H oxidase are the most important pathophysiological mechanisms. Also, the oxidative stress pathway stimulated by angiotensin activates redox-sensitive inflammatory molecules such as AP-1 and NF-κB, which amplify vascular inflammatory response.