Targeting BNIP3 in inflammation-mediated heart failure: a novel concept in heart failure therapy.
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.
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Patrick Asare
PA
Fordjour
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Lingyang
L
Wang
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Hui
H
Gao
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Lan
L
Li
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Yadong
Y
Wang
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Makafui
M
Nyagblordzro
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Kojo
K
Agyemang
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, # 312 Anshanxi Road, Nankai District, Tianjin, 300193, China. fgw1005@hotmail.com.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. fgw1005@hotmail.com.|Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. fgw1005@hotmail.com.
Guanwei
G
Fan
D000818:Animals; D017209:Apoptosis; D018390:Gene Targeting; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C090121:BNIP3 protein, human; C505650:BNIP3 protein, rat; D018836:Inflammation Mediators; D015850:Interleukin-6; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha
BNIP3; Endoplasmic reticulum calcium; Heart failure; Inflammation