User:Swasti95/HSP70

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HSP70 in cardiovascular diseases

HSP70 is a chaperone with ubiquitous presence[6]. It is crucial in the cardiovascular system. HSP70 normally aids in protein folding and aggregation; when present in the cell, functioning as an anti-inflammatory molecule; however, under stress conditions, it is localized to the extracellular milieu, where it is involved in inducing inflammatory pathways and contributes to disease pathogenesis[10]. It is well established that intracellular HSP70 (iHSP70) levels play a protective role, whereas extracellular HSP70 (eHSP70) levels in circulating blood are linked to pathophysiology in micro and microvasculature, which results in a variety of cardiovascular illnesses.HSP70 homologues identified in human cytosol includes HSPA1A, HSPA1B, HSPA1L, HSPA12B, HSPA13,HSPA14 whereas HSPA9 in mitochondria.The HSP70 acts as DAMP and activates innate immune response which as involved in cardiovascular disease progression[9].

The chaperone protein acts as auto antigen in atheroscelorsis.Increased oxidative stress causes the formation of high density oxidized LDL, the first event in the formation of plaque.This activates HSP70 and its promoter in the endothelial and smooth muscle cells, which contributes to atherosclerosis by inducing JAK/STAT pathway expression[5][7]. Elevated levels of HSP70 in the serum were largely associated with increased calcification in patients with chronic heart failure, peripheral and renal vascular diseases[8].

The fluctuations in the levels of chaperone HSP70 affect the homeostasis. Diabetes leads to several microvasculature and microvasculature diseases like retinopathy, Toll like receptors are integral part of innate immune system and eHSP70 binds to toll like receptors and activates the MyD88 pathway, further stimulating NF-kB, cytokines like TNFα and IL1 β , increased production of  reactive oxygen species contributing to insulin resistance and diabetes. Whereas there is decrease in the levels of iHSP70 [1].

HSP70 is also linked to high blood pressure, a worldwide concern and risk factor for a variety of cardiovascular diseases. Hypertension causes endothelial dysfunction and vascular wall damage, both of which contribute to arterial stiffness and atherosclerosis. HSPA1A, HSPA1B, and HSPA1L are three genes in humans that encode HSP70, and their polymorphism is linked to the onset of high blood pressure and cardiovascular disease [4]. Angiotensin II, endothelin-1, or phenylepinephrine cause HSP70 overexpression, which activates several molecular pathways, resulting in increased production of ROS, CRP, IL-10, TNF-alpha, and IL-6 [3][4]. These inflammatory signals interfere with the antioxidant machinery and results in rapid disease progression.

HSP70 expression increases after the coronary bypass surgery. Exercise has a positive and protective impact on cardiovascular disorders and stimulates the increased production of chaperone protein together known to be cardioprotective.