In this review, we discuss the mechanisms how this prototypical scaffold protein organizes signalosomes responsible for the regulation of class IIa histone deacetylases and cardiac transcription factors such as NFAT, MEF2, and HIF-1α, as well as how this signalosome represents a novel therapeutic target for the prevention or treatment of heart failure.
Transplantation of either HIF-1α-modified CSCs or single CSCs reduced cardiomyocyte apoptosis in rats with heart failure after MI, promoted vascular regeneration in infarct area, and improved cardiac function.
Tafazzin-deficient mice hearts display reduced HIF-1α levels and undergo maladaptive hypertrophy with heart failure in response to pressure overload challenge.
These results collectively suggest that in the pressure overload heart failure model, HSF1 promoted formation of macrophages by inducing upregulation of HIF-1 expression, through which heart failure was ameliorated.
In this review, summarizing the "President's Distinguished Lecture Award" of XX World Congress of International Society for Heart Research 2010 in Kyoto, Japan, we introduce recent our studies on HF, including 1) p53-induced suppression of Hif-1-induced angiogenesis as a novel mechanism of HF, 2) angiogenesis as a potential therapeutic strategy for HF, and 3) IGFBP-4 as a novel factor for cardiomyogenesis by inhibiting canonical Wnt signaling.
We hypothesized that the frequency of GT(n) repeats in pediatric heart failure (HF) reflects plasma biomarkers of different disease processes: the soluble receptor for advance glycation end products (sRAGE, marking cellular activation), oxLDL (oxidative stress), NGAL (impaired renal function), HIF-1α (hypoxia) and hsCRP (inflammation).
Our findings show a crucial role of LRP1/Pyk2/HIF-1α in hypoxia-induced cardiomyocyte SERCA2 downregulation, a pathophysiological process closely associated with heart failure.
Analysis of animal models suggests that by activation of these homeostatic mechanisms, HIF-1 plays a critical protective role in the pathophysiology of ischemic heart disease and pressure-overload heart failure.
Our investigation concludes that gelsolin is an important contributor to heart failure progression through novel mechanisms of HIF-1alpha and DNase I activation and downregulation of antiapoptotic survival factors.
To test the hypothesis that HIF-1alpha plays a role in the failing myocardium because of volume overload, an aorta-caval shunt was created for 4 weeks in adult Sprague-Dawley rats to induce volume-overload heart failure.