Browsing by Author "Viswanathan, Gayathri"

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    Beta-Arrestins and Receptor Signaling in the Vascular Endothelium.
    (Biomolecules, 2020-12-23) Lee, Claudia; Viswanathan, Gayathri; Choi, Issac; Jassal, Chanpreet; Kohlmann, Taylor; Rajagopal, Sudarshan
    The vascular endothelium is the innermost layer of blood vessels and is a key regulator of vascular tone. Endothelial function is controlled by receptor signaling through G protein-coupled receptors, receptor tyrosine kinases and receptor serine-threonine kinases. The β-arrestins, multifunctional adapter proteins, have the potential to regulate all of these receptor families, although it is unclear as to whether they serve to integrate signaling across all of these different axes. Notably, the β-arrestins have been shown to regulate signaling by a number of receptors important in endothelial function, such as chemokine receptors and receptors for vasoactive substances such as angiotensin II, endothelin-1 and prostaglandins. β-arrestin-mediated signaling pathways have been shown to play central roles in pathways that control vasodilation, cell proliferation, migration, and immune function. At this time, the physiological impact of this signaling has not been studied in detail, but a deeper understanding of it could lead to the development of novel therapies for the treatment of vascular disease.
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    The role of chemokines and chemokine receptors in pulmonary arterial hypertension.
    (British journal of pharmacology, 2019-08-10) Mamazhakypov, Argen; Viswanathan, Gayathri; Lawrie, Allan; Schermuly, Ralph Theo; Rajagopal, Sudarshan
    Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary artery remodelling leading to increased right ventricular pressure overload, which results in right heart failure and premature death. Inflammation plays a central role in the development of PAH, and the recruitment and function of immune cells are tightly regulated by chemotactic cytokines called chemokines. A number of studies have shown that the development and progression of PAH are associated with the dysregulated expression of several chemokines and chemokine receptors in the pulmonary vasculature. Moreover, some chemokines are differentially regulated in the pressure-overloaded right ventricle. Recent studies have tested the efficacy of pharmacological agents targeting several chemokines and chemokine receptors for their effects on the development of PAH, suggesting that these receptors could serve as useful therapeutic targets. In this review, we provide recent insights into the role of chemokines and chemokine receptors in PAH and RV remodelling and the opportunities and roadblocks in targeting them.