Abstract 77: Distinct Profiles of Transient Receptor Potential Canonical (TRPC) Channel Expression in Biventricular Failure

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Kevin J Morine ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Duc T Pham ◽  
Gordon S Huggins ◽  
...  
Keyword(s):  
Heart Failure ◽  
Murine Model ◽  
Transient Receptor Potential ◽  
Human Subjects ◽  
Receptor Potential ◽  
Tissue Samples ◽  
Transient Receptor Potential Canonical ◽  
Biventricular Failure ◽  
Transient Receptor ◽  
End Stage

Heart failure is a major cause of morbidity and mortality. The transient receptor potential canonical (TRPC) family of channels mediate pathologic cardiac remodeling. In particular, TRPC6 participates in a self-propagating circuit that amplifies cardiac hypertrophy and fibrosis. The objective of this study was to explore biventricular expression of TRPCs in advanced heart failure. Methods: Viable left (LV) and right (RV) ventricular free wall tissue was obtained from human subjects with end-stage heart failure (n=12) referred for transplantation or biventricular assist devices. Control LV and RV tissue was obtained from the National Disease Research Interchange (n=3/group). To explore TRPC expression in a murine model, adult male C57BL/6 mice underwent thoracic aortic constriction (TAC) for 10 weeks (n=6/group). Biventricular tissue was analyzed by real-time polymerase chain reaction. Results: Compared to normal LV and RV, levels of TRPC 1, 3, 4 and 6 were increased in failing LV and RV samples, respectively. Levels of TRPC1 and TRPC6 were greater in failing RV than failing LV samples. TRPC 5 and 7 expression were not consistently detected in normal or failing tissue samples. Compared to sham LV, levels of TPRC 1, 4 and 6 increased in the LV after TAC. Compared to sham RV, levels of TRPC 3, 4, and 6 increased in the RV after TAC. Levels of TRPC3 were greater in the RV than LV after TAC. Conclusions: Our results identify distinct profiles of TRPC expression in the RV versus LV in both human tissue and in a murine model of advanced biventricular failure. Levels of select TRPCs are higher in the failing RV compared to LV, suggesting a potentially important role for TRPCs in RV remodeling.

Abstract 11977: Tranilast, Transient Receptor Potential Vanilloid 2 Antagonist, Ameliorates End-Stage Heart Failure of Mice With Dilated Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuko Iwata ◽  
Kazuo Komamura
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Transient Receptor Potential Vanilloid ◽  
End Stage Heart Failure ◽  
Transient Receptor ◽  
Group B ◽  
End Stage

Introduction: Abnormal intracellular Ca2+ handling seems to be involved in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). We have found up-regulation of the expression of transient receptor potential vanilloid 2 (TRPV2), a calcium-permeable cation channel, in the sarcolemma of myocardium of animal and human DCM. Hypothesis: We hypothesized an orally active TRPV2 antagonist, tranilast, ameliorated heart failure symptoms of DCM mice. Methods: We used 4C30 mice (created by National Institute of Biomedical Innovation, Japan), which has abnormal myocardial calcium handling, as a model of DCM. Sixteen 4C30 mice of 25 weeks old with end-stage heart failure were given no drug (control) or 20 mg/kg/day of carvediol (group C) or 400 mg/kg/day of tranilast (group T) or both of them (group B) for 2 weeks. Results: Blood pressure and heart rate were similar among the 4 groups. Echocardiography demonstrated tranilast improved fractional shortening (in %). Control: 6.2±2.5; Group C: 14.2±5.6, NS; Group T: 16.6±2.3, p<0.05; Group B: 17.2±3.2, p<0.05. Tranilast also improved cardiac hypertrophy measured with heart-to-body weight ratio (HW/BW in mg/g). Control: 12.4±2.5; Group C: 11.5±3.4, NS; Group T: 8.6±0.9, p<0.05; Group B: 5.9±1.1, p<0.01. Sarcolemmal expression of TRPV2 measured with immunostaining in 4C30 mice increased twice as much as syngeneic C57BL/6J. Tranilast, not carvedilol, halved the expression of TRPV2, corresponding to reduction in [Ca2+]i of isolated cardiomyocytes. Consistent with those changes, CaMKII phosphorylation reduced in the 4C30 mice after treatment of tranilast. Conclusions: Tranilast ameliorated heart failure symptoms of 4C30 mice, possibly due to the inhibition of Ca2+ influx through TRPV2.

Transient receptor potential canonical channel 1 impacts on mechanosignaling during cell migration

2012 ◽  
Vol 464 (6) ◽  
pp. 623-630 ◽  
Author(s):  
Anke Fabian ◽  
Jessica Bertrand ◽  
Otto Lindemann ◽  
Thomas Pap ◽  
Albrecht Schwab
Keyword(s):  
Cell Migration ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor
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