Adventures in the Adventitia

Abstract

A rterial hypertension, by definition, imparts accrued strain on the vascular wall. This in turn elicits counteracting radial and tangential forces, driving transformations in the vessel wall that aim to accommodate the new conditions and to ultimately restore basal levels of tensile stress. Vascular accumulation of type I, III, and IV collagen in hypertensive patients and in animal models of hypertension effectively counteracts the distending force of blood pressure, but at length it also results in increased vascular stiffness. Clinically, vascular stiffness translates to greater pulse pressure, which is an independent predictor of mortality in patients with end-stage renal failure, hypertension, and diabetes mellitus and in older individuals. 1Conventionally, hypertensive vascular remodeling has been ascribed essentially to smooth muscle cell hypertrophy and amplified collagen synthesis by these cells. However, there is a growing body of knowledge that points to the adventitia as a significant and perhaps even the principal contributor to pathological hypertensive remodeling. In this issue of Hypertension, Bersi et al 2 provide convincing evidence that when it comes to stiffness and stress, we ought to take a closer look at the outer aspect of the arterial wall.Bersi et al 2 found that a 2-or 4-week infusion of angiotensin II (Ang II) in mice, augmenting blood pressure significantly and persistently, resulted in arteries that are both less distensible and less extensible, associated with reduced elastic energy storage. The increased stiffness was attributed essentially to the thickened wall structure. Although smooth muscle hypertrophy and greater deposition of collagen within the lamellae were observed in the aortas of hypertensive mice, the most striking difference between these animals and their normotensive counterparts was in the extent of adventitial fibrillar collagen accumulation. The adventitial collagen was thus considered to bear a greater amount of load under hypertensive conditions compared with normotensive conditions (Figure).These results are reminiscent of and lend strong support to observations made by the same group using a model of carotid artery banding in mice. Both morphological and biaxial mechanical responses were recorded after 6 weeks. In banded arteries, increased pulse pressure and systolic pressure were found to correlate with arterial thickening, adventitial collagen accumulation, as well as decreased axial stretch. 3Moreover, although the media contained a greater fraction of type III collagen, the adventitia contained instead a greater proportion of type I collagen.This latter point is of fundamental importance because there are key differences between medial and adventitial collagen that bear mentioning. For one thing, type III collagen is more extensible than the type I collagen. 4 It forms a relatively elastic network that stores kinetic energy. Perhaps because of this characteristic, the structure of medial collagen changes at the onset of biaxial loading in porcine arteri...

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

“…In response to vascular stress or injury, adventitial cells are often the first to be activated and re-programmed to then influence the tone and structure of the vessel wall, to initiate and perpetuate chronic vascular inflammation, and to act and stimulate the expansion of the vasa vasorum, which can act as a conduit for continued inflammatory and progenitor for cell delivery to the vessel wall [40]. Under conditions of elevated BP, the adventitia becomes the predominant wall component due to the profound influence on intima and media function in disease [40,61]. As so, our work corroborates others' findings and demonstrates the importance of adventitia, suggesting a modulatory role on vascular function [48].…”

Recent Developments in Vascular Adventitial Pathobiology

“…6 Type I is less extensible, helps bear the pressure load, and is an important factor in vascular stiffness. 4,8 The larger adventitial collagen fibers show more diverse orientation under biaxial strain when compared with the smaller medial fibers, which are aligned circumferentially when they are stretched. 9 Studies of in situ coronary arteries show the adventitia to be stiffer than the media in a longitudinal direction while the media takes up the load in the circumferential direction.…”

“…The physiological function of the adventitia was believed to be limited to providing structural support to the blood vessel wall, transporting oxygen and nutrients to the adventitia and outer media of large vessels, and maintaining sympathetic innervation of the vessel wall. 4 These were generally considered physiological static functions and were not believed to play a dynamic role in vascular development and vascular injury and repair. The latter was attributed primarily to the following: i) the endothelial cells (ECs) of the intima, which are located at the blood-vessel wall interface, forming a thromboresistant surface and a selective permeability barrier that becomes dysfunctional in disease; ii) macrophages entering the wall at the luminal side; and iii) smooth muscle cells (SMCs) of the media, which were shown to dedifferentiate and change into several phenotypes in the face of disease.…”

Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice

“…Adventitial layer consists predominantly of type I and III collagens and contributes in the prevention of aortic rupture at high blood pressures, which is accompanied by changing the type I and III ratio. 37 , 38 , 39 The newly synthesized type III collagen, which is susceptible to proteolysis, is increased in human abdominal aortic aneurysm. 40 OPG −/− mice shows the discordant expression of type III collagen in homogenates of whole aorta with its histological distribution at the adventitia, suggesting the distinct synthesis and metabolism in 3 layers of the aortic wall.…”