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Lipids Health Dis. 2014 Oct 22;13:163. doi: 10.1186/1476-511X-13-163.

Improving heart function by modulating myocardiocyte autophagy: a possible novel mechanism for cardiovascular protection of high-density lipoprotein.

Author information

1
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China. yeping301@sina.com.

Abstract

BACKGROUND:

High-density lipoprotein (HDL) has been shown to confer cardiovascular protection in clinical and epidemiologic studies. Emerging evidence suggests that many of the cardioprotective functions of HDL may be due to the phospholipid sphingosine-1-phosphate (S1P).

PRESENTATION OF THE HYPOTHESIS:

HDL-S1P binds to S1P receptors in the heart, activating PI3K/Akt signaling and myocyte survival. PI3K/Akt is a classic signaling modulator of autophagy. Excessive autophagy due to cell death and cardiomyocyte loss may contribute to impaired heart function during pressure overload-induced heart failure. Therefore, we hypothesize that HDL-S1P may suppress excessive autophagy of cardiomyocytes through activation of PI3K/Akt signaling. Further, reconstituted HDL (including S1P) may protect heart function during pressure overload-induced heart failure.

TESTING THE HYPOTHESIS:

We will design the following experiments to test this hypothesis. (1) We will treat cells and mice with PI-3 kinase inhibitors to examine if HDL-S1P downregulates expression of Autophagy-related genes (ATGs) and proteins via activation of PI3K/Akt signaling. (2) We will use siRNA against S1P receptors or inhibitors of S1P receptors to determine which types of S1P receptors participate in this mechanism. (3) We will also examine if reconstituted HDL (including S1P) improves heart function during pressure overload-induced heart failure by suppressing excessive autophagy of cardiomyocytes through activation of PI3K/Akt signaling.

IMPLICATIONS OF THE HYPOTHESIS:

Understanding the autophagy signaling pathway modulated by HDL-S1P will make a major contribution to the field by identifying a novel mechanism for cardiovascular protection of high-density lipoprotein. Further, using reconstituted HDL to improve heart function would provide a novel therapeutic approach for pressure overload-induced heart failure.

PMID:
25339382
PMCID:
PMC4216853
DOI:
10.1186/1476-511X-13-163
[Indexed for MEDLINE]
Free PMC Article

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