Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases.

Predisposition to atherosclerosis and aortic aneurysms in mice deficient in kinin B1 receptor and apolipoprotein E.

Kinin B1 receptor is involved in chronic inflammation and expressed in human atherosclerotic lesions. However, its significance for lesion development is unknown. Therefore, we investigated the effect of kinin B1 receptor deletion on the development of atherosclerosis and aortic aneurysms in apolipoprotein E-deficient (ApoE(-/-)) mice. Mice deficient both in ApoE and in kinin B1 receptor (ApoE(-/-)-B(1)(-/-)) were generated and analyzed for their susceptibility to atherosclerosis and aneurysm development under cholesterol rich-diet (western diet) and angiotensin II infusion. Kinin B1 receptor messenger RNA (mRNA) expression was significantly increased in ApoE(-/-) mice after Western-type diet. Although no difference in serum cholesterol was found between ApoE(-/-)-B(1)(-/-) and ApoE(-/-) mice under Western-type diet, aortic lesion incidence was significantly higher in ApoE(-/-)-B(1)(-/-) after this treatment. In accordance, we observed increased endothelial dysfunction in these mice. The mRNA expression of cyclic guanosine monophosphate-dependent protein kinase I, CD-11, F4/80, macrophage colony-stimulating factor, and tumor necrosis factor-alpha were increased in the aorta of double-deficient mice following Western-type diet, whereas the levels of peroxisome proliferator-activated receptor gamma protein and the activity of matrix metalloproteinase-9 activity were decreased. In addition to the increased atherosclerotic lesions, the lack of kinin B(1) receptor also increased the incidence of abdominal aortic aneurysms after angiotensin II infusion. In conclusion, our results show that kinin B(1) receptor deficiency aggravates atherosclerosis and aortic aneurysms under cholesterolemic conditions, supporting an antiatherogenic role for the kinin B(1) receptor.

Etiopatogenia do aneurisma de aorta abdominal / Etiopathogenesis of abdominal aortic aneurysm

The etiology of the artherosclerotic abdominal aortic aneurysm is still controversial. Different theories developed in independent ways. Probably therefore thedifferent concepts developed independently, and were not considered together to explain the different aspects of the etiology of this peculiar vascular pathology. Recently a tendency appeared to try to put together the different theories since it became clear that etiology of the aneurysm could not be explained by a single ideia. The biomecanical is based upon the fact that the infra-renal abdominal aorta has a tapered fashion, is more rigid than the thoracic aorta and is more prone to suffer the influence of the reflection waves caused by the branches. It has also fewer elastic lamelae in its wall and fewer vessels arising from its vasa vasorum. It seems possible that the artherosclerotic disease contributes to impar the nutrition of the vessel wall. Although the growing rate of an aneurysm is determined by Laplace's law, the ultimate stability of the aneurysm can beexplained by recruitment of collagen fibers, by the progressive rigidity of the wall and by the modification of the geometry of the wall. Mural trombi and smooth muscle fibers do add very little to the wall strength. The theory of the influence of metals in the development of the aneurysm is based upon the clinical and experimental evidences of a participation of the copper metabolism upon the development of aneurysms of the aorta. The genetic theory is based upon the fact that there is probably a familiar tendency for the appearance by an aortic aneurysms. The proteolytic theory explains the aneurysm by an imbalance between proteolysis and anti-proteolysis although the findings of diminishment of elastin and collagen in theaortic wall were not considered to be primary. The most important risc factors such as hipertension and cigarette smoking do probably act as mechanical and metabolic factors. Is is very likely that thete abdominal aortic aneurysm should be explained by an association of a proteolytic and anti-proteolytic imbalance, a genetic predisposition, a structural pesisposition and hemodynamic factors related to the aorto-iliac geometry. HYpertension yn and cigarette smoking doact as worsening factors