Targeting BNIP3 in inflammation-mediated heart failure: a novel concept in heart failure therapy
- 356 Downloads
Myocardial injury activates inflammatory mediators and provokes the integration of BCL-2/adenovirus E1B 19KD interacting protein 3 (BNIP3) into mitochondrial membranes. Translocation of BNIP3 to mitochondria inexorably causes mitochondrial fragmentation. Heart failure (HF) epitomizes the life-threatening phase of BNIP3-induced mitochondrial dysfunction and cardiomyocyte death. Available data suggest that inflammatory mediators play a key role in cardiac cell demise and have been implicated in the pathogenesis of HF syndrome. In the present study, we reviewed the changes in BNIP3 protein expression levels during inflammatory response and postulated its role in inflammation-mediated HF. We also identified inflammatory mediators’ response such as stimulation of TNF-α and NO as potent inducer of BNIP3. Previous studies suggest that the pro-apoptotic protein has a common regulator with IL-1β and induces IL-6-stimulated cardiac hypertrophy. These findings corroborate our contention that interventions designed to functionally modulate BNIP3 activity during inflammatory-mediated HF may prove beneficial in preventing HF. Such a revelation will open new avenue for further research to unravel a novel therapeutic strategy in HF diseases. Moreover, understanding of the relationship between BNIP3 and inflammatory mediators in HF pathologies will not only contribute to the discovery of drugs that can inhibit inflammation-mediated heart diseases, but also enhance the current knowledge on the key role BNIP3 plays during inflammation.
KeywordsBNIP3 Heart failure Inflammation Endoplasmic reticulum calcium
This work was supported by Grant from the National Key Basic Research Program of China (973 Program) (No. 2012CB518404), the National Natural Science Foundation of China (81273891), the National Science and Technology Support Program Projects (2014BAI05B01), and the Program for Changjiang Scholars and Innovative Research Team in University (IRT1276).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animals rights
This article does not contain any studies with human participants or animals performed by any of the authors.
- 4.Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109(21 suppl 1):II-2–II-10Google Scholar
- 5.Libby P (2006) Inflammation and cardiovascular disease mechanisms. Clin Nutr 83(2):456–460Google Scholar
- 21.Chaanine AH, Gordon RE, Kohlbrenner E, Benard L, Jeong D, Hajjar RJ (2013) Potential role of BNIP3 in cardiac remodeling, myocardial stiffness, and endoplasmic reticulum: mitochondrial calcium homeostasis in diastolic and systolic heart failure. Circ Heart Fail 6(3):572–583CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Lee Y, Kubli DA, Hanna RA, Cortez MQ, Lee HY, Miyamoto S et al (2015) Cellular redox status determines sensitivity to BNIP3-mediated cell death in cardiac myocytes. Am J Physiol Cell Physiol 25:00273Google Scholar
- 24.Chinnadurai G, Vijayalingam S, Gibson SB (2009) BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functions. Oncogene 27(S1):S114–S127Google Scholar
- 37.Chiong M, Wang ZV, Pedrozo Z, Cao DJ, Troncoso R, Ibacache M et al (2011) Cardiomyocyte death: mechanisms and translational implications. Cell Death Dis 22(2):130Google Scholar
- 48.Parissis JT, Nikolaou M, Farmakis D, Paraskevaidis IA, Bistola V, Venetsanou K et al (2009) Self-assessment of health status is associated with inflammatory activation and predicts long-term outcomes in chronic heart failure. Eur J Heart Fail 11(2):163–169 Epub 2009/01/27 CrossRefPubMedPubMedCentralGoogle Scholar