Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension

Abstract

Introduction The etiology of varicose veins remains elusive. We hypothesized that abnormal cell cycle events in the vein wall may contribute to changes in the structural integrity, thus predisposing to the development of varicosities. The present study was designed to determine whether or not the same molecular apoptotic pathway exists between great saphenous and splenic veins. Methods Thirty-six samples of diseased splenic veins and varicose great saphenous veins were collected. Twenty-five samples of control splenic and great saphenous veins were also collected. The apoptotic cell proteins expression was immunohistochemically stained with antibodies (anti-Bax and anti-Bcl-xl). Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay and immunofluorescence staining. The morphology of apoptotic cells was observed with an electron microscope. Results The apoptotic ratio in walls (intima and media) of diseased splenic vein and varicose great saphenous vein groups were significantly lower than the corresponding regions in the splenic vein and great saphenous vein groups ( p < 0.01), respectively. A significant difference was not noted in the ratio change of apoptotic cells between the diseased splenic vein and varicose great saphenous vein groups ( p > 0.05). The high positive expression of Bcl-xl proteins was detected in the diseased splenic vein and varicose great saphenous vein groups, respectively. While the high positive expression of Bax proteins was also observed in the splenic vein and great saphenous vein groups, respectively. Electron microscopic observations confirmed that endothelial and smooth muscle cells in diseased splenic vein, varicose great saphenous vein, splenic vein, and great saphenous vein walls exhibited apoptotic morphologic features, such as fuzzy mitochondrial cristae, medullary changes, and margination of the nuclear chromatin. Conclusions Our results showed the same dysregulation of apoptosis via the intrinsic pathway in diseased splenic veins and varicose great saphenous veins. This observational study suggests that apoptotic down-regulation in the veins wall is a cause of diseased splenic veins and varicose great saphenous veins, but does not exclude the possibility that other mechanisms are involved.

The aging venous system: from varicosities to vascular cognitive impairment

“…Increased presence of apoptotic endothelial and smooth muscle cells was documented in varicose veins removed from older patients [40]. Recent observations confirmed the presence of apoptotic cells in the venous wall in chronic venous insufficiency [237].…”

TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension

“…In vessels, immature vascular smooth muscle cells (VSMCs) are prone to proliferation, migration and synthesis of ECM components (5). The apoptotic decrease of portal vein smooth muscle cells (PVSMCs) in the vein wall is a cause of portal vein remodeling in PHT (6). Currently, there are no approved therapeutic options designed to reverse the progression of PHT.…”

Varicose veins: on the verge of discovering the cause?

“…Как и многие другие процессы в венозной стенке, это событие имеет как молекулярные, так и генетические причины. Среди них гиперэкспрессия антиапоптотического гена BCL2, что вызывает изменение баланса между индукторами и ингибиторами апоптоза [30][31][32]. Секреция BCL2 может усиливаться при гипоксии стенки вены из-за ее перерастяжения и сдавления vasa vasorum [31,33].…”