scholarly journals Chemogenetic activation of intracardiac cholinergic neurons improves cardiac function in pressure overload-induced heart failure

2020 ◽  
Vol 319 (1) ◽  
pp. H3-H12 ◽  
Author(s):  
Jhansi Dyavanapalli ◽  
Aloysius James Hora ◽  
Joan B. Escobar ◽  
John Schloen ◽  
Mary Kate Dwyer ◽  
...  

Intracardiac ganglia form the final common pathway for the parasympathetic innervation of the heart. This study has used a novel chemogenetic approach within transgenic ChAT-Cre rats [expressing only Cre-recombinase in choline acetyl transferase (ChAT) neurons] to selectively increase intracardiac cholinergic parasympathetic activity to the heart in a pressure overload-induced heart failure model. The findings from this study confirm that selective activation of intracardiac cholinergic neurons lessens cardiac dysfunction and mortality seen in heart failure, identifying a novel downstream cardiac-selective target for increasing cardioprotective parasympathetic activity in heart failure.

2019 ◽  
Vol 125 (Suppl_1) ◽  
Author(s):  
Yoshifumi Okawa ◽  
Atsushi Hoshino ◽  
Tomoya Kitani ◽  
Ryoetsu Yamanaka ◽  
Daichi Hato ◽  
...  

2010 ◽  
Vol 32 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Kristopher M. Cumbermack ◽  
Jun Cheng ◽  
Yibing Nong ◽  
William T. Mahle ◽  
Ronald W. Joyner ◽  
...  

2016 ◽  
Vol 37 (4) ◽  
pp. 473-482 ◽  
Author(s):  
Chun-kai Huang ◽  
Bi-yi Chen ◽  
Ang Guo ◽  
Rong Chen ◽  
Yan-qi Zhu ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Endong Ji ◽  
Tiantian Jiao ◽  
Yunli Shen ◽  
Yunjia Xu ◽  
Yuanqing Sun ◽  
...  

Evidences abound that HSF1 and ALDH2 are of cardioprotective effect, yet there is still no report on whether HSF1 can regulate ALDH2 to delay the occurrence of heart failure. We first established the pressure overload-induced heart failure model of mice by transverse aortic constriction (TAC) and discovered that, in the forming period of heart failure, changes of HSF1 and ALDH2 expression recorded the consistent trend. When HSF1 was upregulated/downregulated to delay/promote the occurrence of heart failure, PKC and ALDH2 also showed increased/decreased expression. And when ALDH2 was upregulated/downregulated, the role of HSF1 in delaying the occurrence of heart failure strengthened/weakened. Next, we used mechanical stretch to establish a pressure-stimulated myocardial hypertrophy model and discovered an increased expression of both HSF1 and ALDH2. When HSF1 was upregulated/downregulated to increase/decrease the expression of myocardial hypertrophy gene beta-MHC, PKC and ALDH2 recorded an increased/decreased expression. When an inhibitor was used to downregulate the expression of PKC in cardiomyocytes, we found that the role of HSF1 in upregulating ALDH2 beta-MHC weakened. These findings suggest that HSF1 can upregulate the expression of ALDH2 via PKC to promote pressure-stimulated myocardial compensatory hypertrophy, which is an important molecular pathway for HSF1 to ameliorate heart failure.


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