Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function

Area of Science:

• Cardiovascular Research
• Mitochondrial Biology
• Pharmacology

Background:

• Myocardial mitochondrial dysfunction is a primary driver of chronic heart failure (CHF).
• Key factors include increased reactive oxygen species (ROS), impaired mitochondrial biogenesis, disrupted mitochondrial calcium ([Ca2+]m) homeostasis, and reduced mitochondrial membrane potential (ΔΨm).
• Targeting mitochondrial function offers a promising therapeutic strategy for CHF.

Purpose of the Study:

• To investigate the effects of pyrroloquinoline quinone (PQQ) on mitochondrial function in a cardiac pressure overload model.
• To elucidate the mechanism by which PQQ regulates mitochondrial calcium ([Ca2+]m) homeostasis.

Main Methods:

• Cardiac pressure overload induced by transaortic constriction (TAC) in Sprague Dawley rats.
• In vitro experiments using neonatal rat left ventricle myocytes (NRVMs) treated with angiotensin II (Ang II).
• Assessment of cardiac remodeling, mitochondrial morphology, mitochondrial biogenesis markers (PGC-1α, TFAM), mitochondrial membrane potential (ΔΨm), ROS levels, and mitochondrial calcium ([Ca2+]m) handling proteins (NCLX, MCU).

Main Results:

• PQQ administration improved pressure overload-induced cardiac remodeling and cardiomyocyte hypertrophy, preventing CHF.
• PQQ preserved mitochondrial morphology and counteracted the downregulation of PGC-1α and TFAM.
• PQQ reduced ROS levels, increased ΔΨm, and normalized [Ca2+]m homeostasis by upregulating NCLX expression.

Conclusions:

• PQQ prevents mitochondrial calcium overload by enhancing NCLX expression, thereby reducing ROS and protecting ΔΨm.
• PQQ promotes mitochondrial biogenesis by increasing PGC-1α and TFAM expression.
• These actions collectively protect against mitochondrial dysfunction and reduce cardiac damage in pressure overload-induced heart failure.