Maintaining PGC-1α expression following pressure overload-induced cardiac hypertrophy preserves angiogenesis but not...

Area of Science:

• Cardiovascular Biology
• Mitochondrial Medicine
• Molecular Cardiology

Background:

• Pathological hypertrophy involves repressed peroxisome proliferator-activated receptor coactivator 1α (PGC-1α), reduced mitochondrial oxidative capacity, and impaired fatty acid oxidation (FAO).
• Maintaining PGC-1α may offer a therapeutic strategy against cardiac dysfunction.

Purpose of the Study:

• To investigate if elevated PGC-1α levels can preserve mitochondrial function and prevent contractile dysfunction during pressure overload hypertrophy (POH).

Main Methods:

• Transverse aortic constriction (TAC)-induced POH in mice overexpressing PGC-1α (TG) and nontransgenic controls (Cont).
• Assessed PGC-1α levels, FAO and oxidative phosphorylation (oxphos) gene expression, mitochondrial function, ATP synthesis, cardiac contractility, capillary density, VEGF expression, apoptosis, and fibrosis.

Main Results:

• TG mice showed sustained PGC-1α levels and prevented repression of FAO and oxphos genes post-TAC.
• Despite this, mitochondrial function, ATP synthesis, and contractile function were equally impaired in TG and Cont mice after TAC.
• Capillary density was preserved, VEGF expression increased, and apoptosis and fibrosis were reduced in TG mice post-TAC.

Conclusions:

• Sustaining physiological PGC-1α levels during POH preserves myocardial vascularity and reduces adverse remodeling.
• However, it does not prevent the impairment of mitochondrial function or contractile dysfunction in pathological cardiac hypertrophy.