Polypill to protect against cardiovascular dysfunction, including cardiac hypertrophy and fibrosis: A four-component Polypill consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg) or Valsartan (40 mg) [Polypill-HAAE/HAAV] 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, 30/August/2019, 12.03 am

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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 16+), by Prof. Dr. Stefan Hanns Engelhardt PhD., 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: Polypill to protect against cardiovascular dysfunction, including cardiac hypertrophy and fibrosis: A four-component Polypill consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg) or Valsartan (40 mg) [Polypill-HAAE/HAAV] 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 upregulation of its target gene

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From the 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 the Wnt pathway and improve cardiac function by attenuating cardiac hypertrophy and pathologic fibrosis.


From Research Findings to Therapeutic Opportunity:

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 each year by 2030, 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.


From Research Findings to Therapeutic Opportunity

A study from the Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreaticobiliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran and others shows that “Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. This study was published, in the 24 August 2019 issue of of the prestigious journal Lancet (Impact factor: 53+)by  Prof. Malekzadeh R, M.D., Roshandel G Ph.D., and others. This study suggests that  patients who consumed a four-component Polypill consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg)  or Valsartan (40 mg) are associated with reduced risk of  major cardiovascular events.  However, the precise mechanism of action the four-component polypill remains unclear. 

The study presented here substantiates and supports the aforementioned study’s’ claim, and others, by providing detailed mechanistic insights into how Polypill-HAEE attenuates and protects against myocardial dysfunction, including cardiac hypertrophy, fibrosis of the myocardium, cardiac ageing and myocardial infarction.

Polypill-HAAE/HAAV, 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 the 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 subjecting cardiac patients to undergo Polypill-HAAE/HAAVbased therapy, one may prevent pathological cardiac hypertrophy and fibrosis of the myocardium.

 

Figure 1. Polypill-HAEE functions as a Cardioprotective agent. Mechanistic insights into how Polypill-HAEE decreases the expression of MiR-29 and attenuates cardiac hypertrophy and fibrosis.

Figure 2. Polypill-HAEE  attenuates cardiac hypertrophy and fibrosis through down-regulation of MiR-29 and up regulation of genes that promote cell cycle, including cyclins.

Figure 3. The chemical structure of  the constituents of Polypill-HAEE. It consists of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg).  Polypill-HAEE attenuates cardiac hypertrophy and fibrosis through down-regulation of MiR-29.

Figure 4. The chemical structure of the constituents of Polypill-HAAV. It consists of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Valsartan (40 mg).  Polypill-HAAV attenuates cardiac hypertrophy and fibrosis through down-regulation of MiR-29 (Updated on 30 Aug 2019 at 10.07 pm).

Figure 5. While it had been shown that  in vivo silencing or genetic deletion of miR-29  attenuates cardiac fibrosis and cardiac hypertrophy, the study presented here suggests, for the first time, that,  Polypill-HAEE decreases the expression of MiR-29, and attenuates cardiac dysfunction. And, thereby, it makes those who take Polypill-HAEE less susceptible to cardiac dysfunction.

Figure 6. While it had been shown that  intake of Polypill-HAEE reduces the risk of major cardiac events, the mechanistic basis of which remains largely unclear.  The study presented here, suggests, for the first time, that,  Polypill-HAEE decreases the expression of MiR-29, and attenuates cardiac dysfunction. And, thereby, it makes those who take Polypill-HAEE less susceptible to major cardiac events.

Together, the study presented here, provides, for the first time, plausible explanation and mechanistic and functional insights into how Polypill-HAAE/HAAV may attenuate the risk of cardiac dysfunction.

Thus, those who are above 55 years, by taking Polypill-HAAE/HAAV, they may prevent ageing-associated (or, stress-associated) decline in cardiac function and cardiac dysfunction (fig. 2). Together, this study provides, for the first time, mechanistic and functional insights into how Polypill-HAAE/HAAV may protect against cardiac dysfunction and heart failure in the long-term (figs. 4-5).  

Finally, this study suggests, for the first time, that Polypill-HAAE/HAAV, either alone or in combination with other cardioprotective drugs,” may be used to improve cardiac function and protect against cardiovascular dysfunction.

Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by:

Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed mechanistic information: How does Polypill-HAAE/HAAV decrease the expression of MiR-29?

Amount: $ 1, 500#

# Research cooperation

For purchase and payment details, you may reach us at admin@genomediscovery.org


References:

Web:http://genomediscovery.org or http://newbioideas.com/

Citation: Boominathan, L., Polypill to protect against cardiovascular dysfunction, including cardiac hypertrophy and fibrosis: A four-component Polypill consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg) or Valsartan (40 mg) [Polypill-HAAE/HAAV] 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 upregulation of its target gene, 30/August/2019, 12.02 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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