Written by Joyce Smith, BS. In a rat model, researchers demonstrated that pyrroloquinoline quinone (PQQ) has the ability to stimulate mitochondrial biogenesis to prevent cardiac damage and promote heart health.
Mitochondria are the energy source in the human cell and regulate cellular metabolism, providing energy to sustain every heartbeat 1; however, in patients with heart failure, they can wear out like an old battery 2. Mitochondrial dysfunction and heart failure (due to cardiac pressure overload) can trigger vicious cycles 3 of increased reactive oxygen species (ROS) levels, disruption of mitochondrial biogenesis and mitochondrial Ca2+([Ca2+]m) homeostasis, reduction of the mitochondrial membrane potential (ΔΨm) and increased mitochondrial permeability 2,4. Therefore, preventing mitochondrial dysfunction may be an effective treatment for chronic heart failure 5.
PQQ, present in plant and animal tissues, is a strong antioxidant cofactor in the reduction oxidation process. This study 6 investigated the effects of PPQ on mitochondrial function in a cardiac pressure overload model, to determine the mechanism by which PQQ regulates [Ca2+]m homeostasis .To determine the effect of PPQ on chronic heart failure and systolic function in vivo, old rats were subjected to either sham or transaortic constriction (TAC) surgery. Both groups were administered intragastrically a daily dose of 0.4, 2, or 10 mg/kg of PPQ for a 12-week duration. Heart/body weight ratios, left ventricular ejection fraction, and failure markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), were measured.
After 12 weeks of TAC, rats showed significant ventricular and myocyte hypertrophy and increased heart/body weight ratios. Both the 2 and 10 mg PQQ treatments had good therapeutic effects; however, the 10 mg PQQ/km body weight showed no concentration-dependent effect, thus the 2mg dose was determined to be the best therapeutic dose among the three groups.
Further testing of the 2mg PQQmg/kg body weight dose revealed a positive effect of PQQ in the in vivo model. PQQ’s in vivo testing on the (TAC + 2mg PQQ) and the (TAC only) groups, revealed that only the TAC group showed signs of ventricular myocyte enlargement and fibrosis, collagen deposition (the hallmark of cardiac hypertrophic remodeling) and increased mRNA expression of heart failure markers ANP and BNP, whereas, in the TAC +2mg PQQ group, these effects were all significantly reduced. Testing of isolated hearts in an in vitro model of cultured neonatal rat ventricular myocytes (NRVMs) treated with angiotensin to simulate a cardiac pressure overload, further validated PQQ’s ability to counter the effects of cardiac remodeling. Pretreatment with 10 and 100 μM PQQ reversed the changes in ANP and BNP mRNA expression and the surface area of NRVMs by preventing mitochondrial biogenesis changes (morphological changes in the heart mitochondria caused by cardiac pressure overload and increased reactive oxygen species [ROS] production). When investigating the mechanism by which PQQ regulates [Ca2+]m homeostasis, researchers found that PQQ can prevent [Ca2+]m overload by increasing the mitochondrial Na+/Ca2+ exchanger (NCLX) expression, thereby reducing ROS production and protecting the mitochondrial membrane potential (ΔΨm).
In this study, PQQ demonstrated an ability to improve pressure overload-induced cardiac remodeling and cell hypertrophy, to regulate ROS levels and to increase mitochondrial membrane potential which collectively may slow or help prevent the occurrence of chronic heart failure. The research team plans to continue their exploration of PQQ’s health benefits in their next study.
Source: Xu, Xuan, Chu Chen, Wen-Jiang Lu, Yi-Ling Su, Jian-Yu Shi, Yu-Chen Liu, Li Wang, Chen-Xi Xiao, Xiang Wu, and Qi Lu. “Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function.” Cardiovascular Diagnosis and Therapy 10, no. 3 (2020): 453.
This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-No Derivs 4.0 International License (CC BY-NC-ND 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Posted August 26, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- Kumar AA, Kelly DP, Chirinos JA. Mitochondrial Dysfunction in Heart Failure With Preserved Ejection Fraction. Circulation. 2019;139(11):1435-1450.
- Zhou B, Tian R. Mitochondrial dysfunction in pathophysiology of heart failure. J Clin Invest. 2018;128(9):3716-3726.
- Chaanine AH, Joyce LD, Stulak JM, et al. Mitochondrial Morphology, Dynamics, and Function in Human Pressure Overload or Ischemic Heart Disease With Preserved or Reduced Ejection Fraction. Circulation Heart failure. 2019;12(2):e005131.
- Ribeiro Junior RF, Dabkowski ER, Shekar KC, KA OC, Hecker PA, Murphy MP. MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload. Free radical biology & medicine. 2018;117:18-29.
- Murphy MP, Hartley RC. Mitochondria as a therapeutic target for common pathologies. Nature reviews Drug discovery. 2018;17(12):865-886.
- Xu X, Chen C, Lu WJ, et al. Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function. Cardiovascular diagnosis and therapy. 2020;10(3):453-469.
