Cardiovascular problems are major cause of death and morbidity in diabetes. Hyperglycemia is a significant factor in progression of micro and macro-vascular complications in diabetic patients1.
In recent reports it has been demonstrated that gap junction intercellular communication (GJIC) plays an important role in cardiovascular tissue homeostasis2. Gap Junctions are membrane channels within cells that help connecting cytoplasm of two neighboring cells, to exchange metabolites, ions and second messengers. They are composed of connexins (Cxs), a large family of trans-membrane proteins2.
Vascular endothelial GJIC is mediated by the Cx proteins which are involved in maintenance of endothelial function3. Endothelial dysfunction is considered a major threat factor of cardiovascular complications in diabetes.
Previous reports had shown that elevated glucose level alters the connexin expression (Gap junction function) in various types of vascular endothelial cells. This may lead to endothelial cell dysfunction in diabetes4.
On the other hand, petite information is available about the effect of high glucose on connexin expression and GJIC function in macro-vascular endothelial cells. Therefore, researchers conducted a study in which they investigated the effects of different high glucose concentrations on connexin level and GJIC activity in cultured human umbilical vein endothelial cells (HUVECs) 5.
For this purpose researchers used Rutaecarpine, an active ingredient of Chinese herbal medicine. It exerts many cardiovascular biological effects which are proved to be related to activation of the Transient Receptor Potential Vanilloid subtype 1 (TRPV1)6. This TRPV1 is mainly distributed in the terminals and cell bodies of sensory neurons and also wildly presented in non-neurons tissues, such as vascular endothelial cell7.
Recently it has been found that rutaecarpine attenuates endothelial dysfunction in cultured HUVECs. These protective effects are related to the regulation of connexins expression and improvement of GJ function in endothelial cells. These effects can be blocked by a competitive TRPV1 antagonist, suggesting the key role of TRPV1 in the protective effects of rutaecarpine8.
So the researchers took Human umbilical vein endothelial cells (HUVECs) and treated them with different concentrations of high glucose. The protein level of connexin was detected by western blot. The GJ function of endothelial cells was measured by scrape-loading dye transfer experiments. Endothelial cell function was evaluated by cell viability assays.
It was concluded that high glucose reduced Cx37 (connexin) protein level, leading to GJIC dysfunction in HUVECs. Rutaecarpine prevented high glucose-induced endothelial dysfunction by recovering Cx37 GJIC function via activation of TRPV1.
Written by: Rabeeia
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17 November, 2019