The Role of Endothelial Dysfunction in Aortic Aneurysms

Abstract

Abdominal aortic aneurysm is a vascular disease which, despite the fact that it shares common risk factors with atherosclerosis, develops in parallel but as a partly independent process, through different pathogenic mechanisms. The pathogenic mechanisms involve metalloproteinase and collagenase activation, median and adventitial degradation, elastin lysis, vascular smooth cells transformation and apoptosis, collagen production and lysis imbalance combined with excessive inflammatory infiltration. Endothelial cells respond to a number of stimulating factors, including smoking, hypertension and AT1 receptor stimulation and non-uniform distribution of wall stress. Their ability to produce NO is crucial in order to adapt. Endothelial cells contribute to AAA development due to increased oxidative stress which is partly mediated by impaired NO bioavailability due to endothelial dysfunction and NADPH oxidase overexpression. In addition, they express several molecules among which adherence molecules, selectins, endothelin-1, regulating inflammatory infiltration and oxidative stress. Inflammatory cells consist of monocytes, polymorphonuclear neutrophils and lymphocytes and they are involved in the degrading process in the aortic wall by secreting proteolytic enzymes or by releasing interleukins which mediate the inflammation response. Endothelial dysfunction and arterial stiffness reflect on indices like FMD, carotid-femoral PWV and augmentation index, sometimes with controversial results. At present, surgical treatment is the only option provided in patients with large AAA, in particular. Focusing on the emerging role of endothelial cells in AAA pathology may contribute in creating new therapeutic options in a disease which has not yet a well-accepted, implemented pharmaceutical treatment.

The hypertension of hemophilia is associated with vascular remodeling in the joint

“…We emphasize that it remains unclear whether vascular remodeling in the hemophilic joint is a cause or a consequence of the hypertension, but speculate that these conditions fuel a vicious cycle of events that also include bleed perpetuation. It is well documented that chronic hypertension causes altered vessel wall characteristics in microvascular beds such as the kidney, retina, or brain [10][11][12][13] , triggering hemorrhages and aneurysms 11,[48][49][50][51][52] While these observations are consistent with the hypothesis that vascular remodeling and blood pressure dynamics are linked in PWH, other yet unrecognized hemophilia-specific factors may emerge from future investigations. As neither Pettersson score nor HJHS was associated with SBP or DBP, more simple explanations, such as painful deteriorating joints, do not seem to play a major role.…”

“…We emphasize that it remains unclear whether vascular remodeling in the hemophilic joint is a cause or a consequence of the hypertension, but speculate that these conditions fuel a vicious cycle of events that also include bleed perpetuation. It is well documented that chronic hypertension causes altered vessel wall characteristics in microvascular beds such as the kidney, retina, or brain, triggering hemorrhages and aneurysms. Similar microvascular changes may occur in hemophilic joints with altered and proliferating soft tissues in response to hemarthrosis.…”

CTRP9 induces mitochondrial biogenesis and protects high glucose-induced endothelial oxidative damage via AdipoR1 -SIRT1- PGC-1α activation

“…It has been considered that vascular endothelial dysfunction and impaired vascularization are contributed to the occurance and development of diabetic vascular complications [14]. Endothelial dysfunction is influenced by many factors [15].…”

Long-term Survival Rates for Patients with Aortic Aneurysm

“…11 Endotherial cells respond to a number of stimulating factors such as smoking. 12 Therefore, aggressive non-smoking education program should be applied in smoking AA patients. However, a study in an England cohort from 1997 through 2010…”