Vinpocetine protects against the development of experimental abdominal aortic aneurysms

Abstract

Abdominal aortic aneurysm (AAA), commonly occurring in the aged population, is a degenerative disease that dilate and weaken infrarenal aorta due to progressive degeneration of aortic wall integrity. Vinpocetine, a derivative of alkaloid vincamine, has long been used for cerebrovascular disorders and cognitive impairment in the aged population. Recent studies have indicated that vinpocetine antagonizes occlusive vascular disorders such as intimal hyperplasia and atherosclerosis. However, its role in vascular degenerative disease AAA remains unexplored. Herein, we determined the effect of vinpocetine on the formation of AAA as well as the intervention of pre-existing moderate AAA. AAA was induced by periaortic elastase application in C57BL/6J mice. Systemic vinpocetine treatment was applied daily via intraperitoneal injection. We showed that vinpocetine pre-treatment remarkably attenuated aneurysmal dilation assessed by diameter and volume. More importantly, vinpocetine also significantly suppressed the progression of pre-existing moderate AAA in a post-intervention model. Vinpocetine improved multiple cellular and molecular changes associated with AAA, such as elastin degradation, media smooth muscle cell depletion, collagen fibers remodeling and macrophage infiltration in aneurysmal tissues. Vinpocetine potently suppressed TNF-α-induced NF-κB activation and proinflammatory mediator expression in primary cultured macrophages in vitro, as well as in the aorta wall in vivo, suggesting vinpocetine conferred anti-AAA effect at least partially via the inhibition of inflammation. Taken together, our findings reveal a novel role of vinpocetine in AAA formation, development, and progression. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a novel therapeutic agent for AAA prevention and treatment.

Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm

“…Ten‐week‐old wild‐type C57BL/6J male mice were treated with 0.2% 3‐aminopropionitrile fumarate salt (BAPN) (w/v) in drinking water. 12 Periaortic application of porcine pancreas elastase or heat‐deactivated elastase (sham) were blinded performed on infrarenal abdominal aorta as previously described with slight modifications. 12 Mice were treated with vehicle or sildenafil (100‐mg tablets; Viagra, Pfizer) prepared in drinking water to a concentration of 400 mg/L (0.6 mmol/L) as previously described, 13 resulting in the ingestion of ≈60 to 100 mg/kg per day, starting from the seventh day post‐surgery until harvest.…”

Abdominal Aortic Aneurysm: Roles of Inflammatory Cells

“…Zhang et al. reported that vinpocetine could alleviate AAA development by suppressing TNF-α-induced B cell activation and proinflammatory mediator expression in primary cultured macrophages both in vitro , and in vivo ( 111 ). The interactions of between B cells and other immune cells are illustrated in Figure 2 .…”

“…These dramatically increasing evidences indicate that B cell may be an ideal target to treat AAA patients, and subsequent experiments confirmed this hypothesis. Zhang et al reported that vinpocetine could alleviate AAA development by suppressing TNF-a-induced B cell activation and proinflammatory mediator expression in primary cultured macrophages both in vitro, and in vivo (111). The interactions of between B cells and other immune cells are illustrated in Figure 2.…”

The lipid peroxidation product 4-hydroxynonenal inhibits NLRP3 inflammasome activation and macrophage pyroptosis

“…Nuclear translocation was evaluated using NIH ImageJ software with an intensity ratio nuclei cytoplasm macro. Quantification of translocation was expressed as the percentage of intensity in nucleus over total cell (85). The data points shown are from 3 separate experiments with duplicate or triplicate wells.…”