⇒ Hypertension induced cardiac arrhythmias and heart failure
High blood pressure is a major risk factor for developing cardiac hypertrophy, arrhythmias and heart failure. Current treatment strategy mainly uses anti-hypertensive drugs to lower the blood pressure. However, 30-33% of the treated patients still have blood pressure higher than the recommended level of 140/90 mmHg. Hence finding new effective treatment for hypertension-induced heart diseases is of great importance.
High blood pressure is a major risk factor for developing cardiac hypertrophy, arrhythmias and heart failure. Current treatment strategy mainly uses anti-hypertensive drugs to lower the blood pressure. However, 30-33% of the treated patients still have blood pressure higher than the recommended level of 140/90 mmHg. Hence finding new effective treatment for hypertension-induced heart diseases is of great importance.
Our research on hypertensive heart disease, funded by the American Heart Association and the National Institutes of Health, show that high blood pressure causes elevation of CaMKII activity which, in turn, triggers the development of hypertrophy and heart failure. We are working to identify the molecules responsible for linking mechanical stress to alter the Ca2+-calmodulin-CaMKII signaling. Recently we found, using the Cell-in-Gel system, that (1) mechanical load can induce spontaneous Ca2+ activities that can lead to arrhythmias, and (2) the load-induced arrhythmogenic activities can be suppressed by inhibiting CaMKII.
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Relevant Publications
- Awasthi S, Izu L, Mao Z, Jian Z, Landas T, Lerner A, Shimkunas R, Woldeyesus RA, Bossuyt J, Wood BM, Chen YJ, Matthews DL, Lieu DK, Chiamvimonvat N, Lam KS, Chen-Izu Y, Chan JW. Multimodal SHG-2PF Imaging of Microdomain Ca-Contraction Coupling in Live Cardiac Myocytes. Circ Res. 2015 Dec 7. CIRCRESAHA.115.307919.
- Jian Z, Han H, Zhang T, Puglisi J, Izu LT, Shaw JA, Onofiok E, Erickson JR, Chen YJ, Horvath B, Shimkunas R, Xiao W, Li Y, Pan T, Chan J, Banyasz T, Tardiff JC, Chiamvimonvat N, Bers DM, Lam KS, Chen-Izu Y*. Mechanochemotransduction During Cardiomyocyte Contraction Is Mediated by Localized Nitric Oxide Signaling.Science Signaling (2014) 317:ra27. PMID: 24643800; PMC4103414
- Chen-Izu Y*, Ling Chen, Tamás Bányász, Stacey L. McCulle, Steven M. Scharf, Leighton T. Izu, C. William Balke. Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development. Am J Physiol. (2007) 293(6):H3301-10.