The effect of Connexin43 downregulation on biological functions of HUVEC / 药学学报

Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA (siRNA) to reduce the expression of connexin43 in human umbilical vein endothelial cell (HUVEC), and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by -80% in HUVEC (P < 0.05), and decreased the intercellular communication by -65% (P < 0.05). The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly (P < 0.05), compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.

Targeting angiogenesis and vascular remodeling as a novel therapeutic approach to liver fibrosis / 药学学报

Development of liver fibrosis is closely associated with angiogenesis and abnormal vascular remodeling. Recent studies have highlighted the importance of angiogenesis and vascular remodeling in fibrogenesis, the results that inhibition of angiogenesis is effective in suppression of liver fibrosis demonstrate that therapies with several molecular targets against angiogenesis, inflammation and fibrosis might be beneficial for the treatment of cirrhosis. However, there is some evidence that inhibition of angiogenesis can even worsen fibrosis. This article outlines recent advances regarding the interplay between inflammation, angiogenesis and fibrogenesis in terms of cellular and molecular mechanisms, and suggests a requirement of greater understanding to intervene in these key processes, such as liver sinusoidal endothelial cell fenestration and impact distinct chemokine actions driving monocyte migration and differentiation, for therapeutic benefit in the future.