Hyperthermia treatment prevents angiotensin II-mediated atrial fibrosis and fibrillation via induction of heat-shock protein 72

Novel Strategy to Prevent Atrial Fibrosis and Fibrillation

“…26 Because HSPs are an important family of endogenous protective proteins that increase in response to a wide variety of stresses, including inflammation, 27 we tested the hypothesis that atrial fibrosis and AF evoked by continuous infusion of AII could be prevented by the induction of HSP72. 13 In fact, Mandal et al previously showed that in patients undergoing elective coronary artery bypass surgery, the preoperative HSP72 concentration in right atrial tissue obtained at surgery was higher in patients who did not develop postoperative AF than in those who did develop AF. 28 In cultured rat LA fibroblasts, pretreatment with hyperthermia (42°C for 30 min) was shown to induce HSP72 expression, peaking at 8 h following the application of hyperthermia.…”

“…Based on these observations, they suggested that PPAR-γ activators could become a novel upstream therapy for age-related AF. 22 Thus, pioglitazone has been shown to prevent AF caused by pressure overload, 12 CHF, 13 and aging. 14 It is therefore interesting to evaluate its anti-AF effects in the clinical setting.…”

“…AII-induced extracellular signal-regulated kinase (Erk1/Erk2) phosphorylation, α-SMA expression, TGF-β1 secretion, collagen synthesis, and the expressions of collagen type-1 and tissue inhibitor of metalloproteinases-1 were attenuated in fibroblasts treated with hyperthermia. 13 A small interfering RNA (siRNA) targeting HSP72 could abolish the antifibrotic effects of hyperthermia. 13 Figure 4 illustrates α-SMA expression in fibroblasts by immunocytochemical analysis using laser microscopy.…”

“…13 A small interfering RNA (siRNA) targeting HSP72 could abolish the antifibrotic effects of hyperthermia. 13 Figure 4 illustrates α-SMA expression in fibroblasts by immunocytochemical analysis using laser microscopy. AII caused a remarkable increase in expression of α-SMA in the cytoplasm, when assessed 24 h after AII application.…”

“…10 In this review, we introduce our experimental approaches to the prevention of atrial fibrosis and AF. We have induced atrial fibrosis by pressure overload, 12 continuous infusion of angiotensin II (AII), 13 and 5/6 nephrectomy (5/6Nx). 14 In these 3 AF models, we have evaluated the anti-AF effects of pioglitazone, 12 induction of heat shock protein (HSP), 13 and an antioxidant agent, 14 respectively.…”