Introduction: What they say:
A recent study from the Institute of Pharmacology and Toxicology, Technical University Munich (TUM), 80802, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, 80802, Munich, Germany; and Mount Sinai, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA shows that “Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.” This study was published, in the 20 November 2018 issue of the journal “Nature communications (One of the best journals in general science with an impact factor of 12+), by Prof Engelhardt, Sassi and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Bacillus Calmette Guerin (BCG) vaccine-based adjunct therapy for cardiac hypertrophy and fibrosis: BCG vaccine decreases MiR-29 expression, activates wnt- signaling and its components GSK3B, ICAT/CTNNBIP1, HBP1 and GLIS2, attenuates pathologic hypertrophy, inhibits fibrosis of the heart tissue, and improves cardiac function via up regulation of its target gene
From significance of the study to Public Health relevance:
Given that: (1) cardiovascular disease is the leading cause of death worldwide; (2) the raise of death rate, due to cardiovascular disease, has increased from 123 lakhs in 1990 to 173 lakhs in 2013; (3) 85% of people over 80 years are susceptible to cardiovascular diseases;(4) in India, in 2004, 14.6 lakhs deaths (14% of total deaths) were due to ischemic heart disease; (3) the death due to cardiovascular disease is higher in low-to-middle income countries compared to developed countries; (4) the global economic cost spent in the treatment of cardiovascular disease in 2011 was little more than 10 billion US dollars; (5) an alarming number of people, such as 230 lakhs people, will die from cardiovascular diseases from 2030 onwards; (6) over 240 lakhs people suffer from heart failure globally, with only treatment option being the heart transplant, there is an urgent need to find: (i) a way to induce regeneration of cardiomyocytes that were lost in Myocardial patients; (ii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug.
What is known?
Cardiac stress, in long-term, has been shown to promote pathologic hypertrophy; and fibrosis of the myocardium. Recently, Prof. Engelhardt’s research team has shown that MiRNA-29: (1) augments pathologic hypertrophy; (2) promotes cardiac dysfunction; and (3) deletion or antisense: (a) prevents cardiac hypertrophy; (b) prevents fibrosis; (c) activates the Wnt pathway components, such as GSK3B, ICAT/CTNNBIP1, HBP1 and GLIS2, suggesting that agents that decrease the expression of MiR-29 in adult cardiomyocytes may inhibit wnt pathway and improve cardiac function by attenuating cardiac hypertrophy and pathologic fibrosis.
From Research Findings to Therapeutic Opportunity:
This study suggests, first the first time, Bacillus Calmette Guerin (BCG) vaccine-based therapy, with detailed mechanistic insights, for attenuating cardiac hypertrophy and fibrosis. BCG vaccine has been found to be useful in the treatment of tuberculosis, for more than 100 years, more recently in the treatment of autoimmune diabetes. However, the mechanism of action remains largely unknown.
Tuberculosis (TB) BCG vaccine, by increasing the expression of its target genes, it may decrease the expression of miR-29 (fig.1). Thereby, it may: (1) increase the expression of GSK3B, ICAT/CTNNBIP1, HBP1 and GLIS2; (2) inhibit wnt pathway; (3) increase the expression of a number of other gene products that attenuate cardiac hypertrophy and pathological fibrosis; and (4) prevent cardiac hypertrophy (fig 1). Thus, by vaccinating cardiac patients with BCG vaccine, one may prevent pathological cardiac hypertrophy and fibrosis of the myocardium. Together, this study suggests, for the first time, that BCG vaccine, either alone or in combination with other cardioprotective drugs,” may be used to improve cardiac functions (fig. 2).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by:
Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How does BCG vaccine decrease the expression of MiR-29 and attenuate cardiac hypertrophy and fibrosis?
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Citation: Boominathan, L., Bacillus Calmette Guerin (BCG) vaccine-based adjunct therapy for cardiac hypertrophy and fibrosis: BCG vaccine decreases MiR-29 expression, activates wnt- signaling and its components GSK3B, ICAT/CTNNBIP1, HBP1 and GLIS2, attenuates pathologic hypertrophy, inhibits fibrosis of the heart tissue, and improves cardiac function via up regulation of its target gene, 2/July/2018, 11.13 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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