Starvation Genes Improve and Restores the Failing Heart

In this sepsis induced cardiomyopathy model, carvedilol improves recovery by improving the telomere-p53-pgc signaling.

These 3 gene products are alsoincreased by ursolic acid presumptively by beta hydroxybutyrate.  They are among the 44 starvation genes.

I have previously written how telomerase angiotensin 1-7 are starvation genes that promote metabolically healthy flow mediated dilation which improves small vessel circulation to the healing heart post insult.

See bolded below

http://circ.ahajournals.org/content/134/Suppl_1/A17642.short

Abstract 17642: Carvedilol Improves Prognosis in Sepsis-induced Cardiomyopathy Through the Activation of “telomere-p53-pgc Signaling"

Abstract

Background: Stress-induced cardiomyopathy is a complication of severe sepsis. It is characterized by left ventricular dilatation and depressed ejection fraction. Recent meta-analysis suggested that the mortality depends on the heart hyperkinetic. However, the crucial mechanism of sepsis induced cardiomyopathy and the treatment are still unknown. It has been reported that telomere length has inverse correlation to severity of heart failure and infectious disease. Moreover, it is suggested that dysfunction of “telomere-p53-PGC axis” reduces a mitochondrial function, and as a result, it develops to heart failure.

Purpose: We investigated the therapeutic potential of carvedilol which improves prognosis in preclinical models of severe infection, the murine cecal ligation and puncture (CLP) model to induce peritonitis.

Methods and Results: C57BL/6 male mice were evaluated blood pressure, heart rate and cardiac function followed by CLP surgery and 1mg/kg carvedilol (BB) or saline (CT) was administered for 7days after surgery. 7days after induction of sepsis, BB significantly attenuated blood pressure (101.7±6.0 vs 109.8±57.4mmHg, p<0.05) and heart rate (405.6±18.0 vs 431.6±13.2bpm, p<0.05) as compared to CT. BB also reduced LV dilatation (LVEDV; 53.5±18.5 vs 66.9±15.1uL, p<0.05) and LVEF depression. (61.1±9.9 vs 53.3±7.9%, p<0.05). Kaplan-Meier analysis showed that the 7days mortality significantly reduced in BB group. Telomere shortening of white blood cells seen for sepsis was attenuated in BB by Q-FISH analysis (10.9±1.4 vs 6.8±1.4 telomere fluorescence unit; TFU, p<0.01) Moreover, as compared to CT, BB showed higher expression of tert, PPARγ co-activator (PGC)-1 alpha which promote mitochondrial biogenesis and lower expression of p53 by PCR in heart tissue. Body weight loss was reduced in BB group.

Conclusions: Carvedilol improved sepsis induced cardiomyopathy through the attenuation of telomere shortening due to the enhancement of telomere-p53-PGC axis and reducing mortality resulting from sepsis.