Experimental models for vascular endothelial dysfunction
Vascular endothelial dysfunction is characterized by apoptosis of endothelial cells, an imbalance between vasoconstrictory and vasodilatory substances, the imbalance between ROS and antioxidants, vascular remodeling, loss of vascular integrity which leads to an increased risk of cardiovascular complications. To date, no therapeutic intervention is available as a promising agent. This may be due to a poor understanding of the underlying mechanism involved in vascular endothelial dysfunction in the pathogenesis. Animal models sharing identical features as that of humans are paramount to understand fundamental physiology, mechanism and to explore new targets for developing therapeutic agents. Thus, it becomes mandatory to re-explore the available animal models for a better understanding of molecular pathways involving vascular endothelial dysfunction. The purpose of this paper is to review different models for vascular endothelial dysfunction to the outlook for developing new drugs to treat vascular endothelial dysfunction.
The vascular endothelium is the innermost lining of the blood vessel. It is a metabolically active layer that tends to release various substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function, and platelet adhesion (Sandoo et al., 2010). It plays a crucial role in maintaining vascular tone, integrity, and free flow of the blood under normal physiology. Destruction or injury in the endothelial layer of arteries leads to create an imbalance between vasoconstriction and vasodilatation factors which complicate vascular endothelial dysfunction and lead to cause various other severe cardiovascular disorders. An increase in free radicle production (ROS/RNS), NADPH oxidase, xanthin-oxidase or decrease in glutathione, no generation is the underlying pathways involved in the pathogenesis of vascular endothelial dysfunction. Regulation of inflammatory mediators such as intracellular adhesion molecule-1, von Willi brand factor, Nf-kb and growth factors like endothelin-1, VEGF, PDGF, OLGF, and ILs mutually affect vascular endothelium (Balakumar et al., 2008a). Atherosclerosis, hypertension, hyperglycemia, and smoking are considered to be the self-governing risk factors and foremost determinants in the progression of vascular endothelial dysfunction (Hadi et al., 2005). To identify the potential pharmacological targets for vascular endothelial dysfunction in different experimental models are designed and employed to induce the vascular endothelial dysfunction. Therefore, this paper aims to review various experimental animal models developed to produce vascular endothelial dysfunction.
To understand complex pathogenesis and to develop a new therapeutic alternative for treating vascular endothelial dysfunction animal models are widely used. Continued utilization of these experimental models simulating human vascular endothelial dysfunction, particularly those that combine other clinically relevant comorbidities like obesity, nicotine intake, hyperuricemia or hypercholesterolemia, may open a new vista in development of effective strategies to address the vascular complications. Nevertheless, a restrained methodology is mandatory while experimental find-ings in these models are extrapolated to human vascular endothelial dysfunction.
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