Pressure Overload-Induced Cardiac Dysfunction in Aged Male Adiponectin Knockout Mice Is Associated With Autophagy...

Area of Science:

• Cardiovascular Biology
• Cellular Metabolism
• Molecular Cardiology

Background:

• Heart failure is a major cause of mortality, particularly in elderly, obese, and diabetic individuals.
• Cardiac remodeling significantly contributes to heart failure progression.
• Autophagy plays a crucial role in maintaining cardiac function and remodeling.

Purpose of the Study:

• To investigate the role of adiponectin in cardiac remodeling and function under pressure overload.
• To determine the effect of adiponectin on autophagy in the context of cardiac stress.
• To elucidate the mechanisms by which adiponectin influences cardiac health and dysfunction.

Main Methods:

• Utilized aged adiponectin knockout (Ad-KO) and wild-type (wt) mice subjected to aortic banding for pressure overload (PO).
• Performed cardiac strain analysis via speckle tracking echocardiography.
• Assessed autophagy markers (LC3, p62) and flux using Western blotting and transmission electron microscopy.
• Examined endoplasmic reticulum stress and mitochondrial integrity.
• Investigated adiponectin's direct effect on autophagy flux in H9c2 cardiac myoblasts.

Main Results:

• Ad-KO mice exhibited earlier cardiac dysfunction compared to wt mice after PO.
• Ad-KO mice showed a lack of PO-induced cardiac autophagy, unlike wt mice.
• Mitochondrial degeneration and endoplasmic reticulum stress were associated with impaired autophagy in Ad-KO mice.
• Adiponectin treatment directly enhanced autophagic flux in cardiac myoblasts.

Conclusions:

• Adiponectin directly stimulates autophagic flux in cardiac cells.
• The absence of adiponectin impairs the cardiac autophagy response to pressure overload.
• This impaired autophagy in aged Ad-KO mice contributes to cellular events exacerbating cardiac dysfunction.