Abdominal aortic aneurysm and cerebral aneurysm present different pathological evolutions and responses to pharmacological therapy.
Over-degradation of extracellular components by matrix metalloproteinases (MMPs) has been implicated as an important characteristic during the pathological evolution of the abdominal aortic aneurysm (AAA) and cerebral aneurysm (CA), which contribute to progressive dilation of vascular wall. However, mRNA and protein expression of local rennin-angiotensin system (RAS) components are found down-regulated in CA walls, which is contrary to long-holding concept that local RAS will be activated in response to increased hemodynamic stress and contributes to thickening of arterial wall. Similarly, MMPs inhibition by doxycycline effectively ameliorate AAA expansion in basic and clinical researches, but can not reduce the incidence of CA formation in rat. These evidences may suggest that suppression of RAS favors the regression of AAA, but at an increased risk of CA rupture. As the strategies of RAS blockade have became the optimal antihypertensive drugs of choice in clinical arena, the discrepant responses to pharmacologic intervention of AAA and CA should be received considerable attentions, due to their high prevalence in hypertensive population. Here we proposed that AAA and CA, outward remodeling of elastic and muscular arteries respectively, presented with different pathological evolutions and distinct responses to drug intervention, i.e., RAS and MMPs inhibition. It can not be excluded that the potentially deleterious effects of RAS inhibition on CA may be masked by the beneficial action of controlled blood pressure, and the propagation of CA will be exacerbated once suboptimal dose have been prescribed, or under the condition of stress, even drug withdrawal. If the paradoxical outcomes of these two kinds of arterial remodeling were proven true in basic research, clinical use of RAS blockade should be prudent in hypertensive patients, and routine procedures to detect the existence of CA should be considered. Therefore, in depth investigation in their responses to pharmacological approaches will provide us with more insights into the pathogenesis of arterial aneurysm.
Zhou
Xin
X
Graduate School of Medicine, Tianjin Medical University, Qi-Xiang-Tai Street, Tianjin, China.
Ji
Wen-Jie
WJ
Tu
Yue
Y
Yao
Min
M
Li
Yu-Ming
YM
D001012:Aorta, Abdominal / Q000473:pathology / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004548:Elasticity; D006801:Humans; D002532:Intracranial Aneurysm / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D008955:Models, Cardiovascular