Polypill for Cardioprotection: Polypill-HAAE/HAAV-based therapy for Cardiac repair and myocardial infarction: A four-component  Polypill-HAAE/HAAV consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg)  or Valsartan (40 mg)  increases Agrin expression, activates Yap and ERK-mediated signaling,  replaces scar tissue with functional cardiomyocytes, and promotes cardiomyocyte regeneration and repair after myocardial infarction, via up-regulation of its target gene, 25/September/2019,  8.45 pm

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Introduction: What they say:

A recent study from Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA; and Baylor College of Medicine and The Texas Heart Institute, Houston, Texas 77030, US shows that The extracellular matrix protein Agrin promotes heart regeneration in mice.” This study was published, in the 5 June 2017 issue of Nature, by Prof Tzahor E, Bassat E 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 for Cardioprotection: Polypill-HAAE/HAAV-based therapy for Cardiac repair and myocardial infarction: A four-component  Polypill-HAAE/HAAV consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg)  or Valsartan (40 mg)  increases Agrin expression, activates Yap and ERK-mediated signaling,  replaces scar tissue with functional cardiomyocytes, and promotes cardiomyocyte regeneration and repair after myocardial infarction, 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 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 that heals damaged heart tissue.


What is known?

Prof. Tzahor’s research team has shown recently that: (1) Agrin, one of the components of the neonatal Extracellular matrix (ECM) , promotes regeneration in mouse hearts;  and (2) Agrin promotes cardiomyocytes regeneration after heart attack through disruption of dystrophin-glycoprotein complex and activation of Yap and ERK-mediated signaling,  suggesting that activation of Agrin may: (1) replace  the damaged scar tissue, with functional cardiomyocytes, after myocardial infarction; and (2) protect an individual from myocardial infarction through cardiac rejuvenation and regeneration.


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 those  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)  Polypill-HAEE/V are associated with reduced risk of  major cardiovascular events.  However, the precise mechanism of action of the four-component polypill remains unclear. 

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

This study provides, for the first time, mechanistic insights into how Polypill-HAEE/V may aid in heart regeneration and repair.

Polypill-HAEE/V, by increasing the expression of its target genes, it may increase the expression of Agrin (fig.1). Thereby, it may: (1) inhibit dystrophin-glycoprotein complex;(2) increase Yap and ERK-mediated signaling; (3) increase the expression of gene products that promote cardiac regeneration and survival;(4) increase the expression of miRNAs that promote cardiac regeneration and survival;(5) increase cardiomyocyte proliferation; (6) replace scar tissue with heart muscle functional  cardiomyocytes; (7) promote cardiomyocyte survival/regeneration; (8) promote recovery after myocardial infarction; and (9) extend lifespan (fig 1).

Thus, by treating myocardial patients with Polypill-HAEE/V or its analogs or functional or mechanistic equivalents of its analogs, cardiologists may preserve myocardial function after myocardial infarction; and prevent ageing-associated (or, stress-associated) decline in cardiac function. Together, this study suggests, for the first time, that pharmacological formulations encompassing Polypill-HAEE/V  or its analogs, either alone or in combination with other drugs,” may be used to heal the damaged cardiac tissue after myocardial infarction (fig. 2).

In conclusion, this study suggests, for the first time, with detailed mechanistic insights, that pharmacological formulations encompassing 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]   or its analogs or functional equivalents that share their mechanism of action, either alone or in combination with any of the known compounds that improve myocardial function,” may be used to heal damaged cardiac tissue, and repair and regenerate new cardiomyocytes after myocardial infarction (fig.2).

Figure 1. Mechanistic insights into how 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] promotes heart regeneration and repair. Polypill-HAAE induces the expression of Agrin and other genes that promote cardiac regeneration and repair to prevent myocardial infarction and diabetic cardiomyopathy.

Figure 2. Polypill-HAAE-based therapy for myocardial diseases. Polypill-HAAE may aid in heart regeneration and repair through induction of Agrin and other genes.

Figure 3. Polypill-HAAE-based therapy for myocardial diseases. Polypill-HAAE may aid in heart regeneration and repair through induction of Agrin and other genes.

Figure 4. Polypill-HAAV-based therapy for myocardial dysfunction. Polypill-HAAE/HAAV may aid in heart regeneration and repair through induction of Agrin and other genes.

Figure 5. While it had been shown earlier that Polypill-HAAE/HAAV promotes cardiac regeneration after myocardial infarction, its mechanism of action remains unclear. The study presented suggests that Polypill-HAAE/HAAV may aid in heart regeneration and repair through induction of Agrin and other genes.

Figure 6. While it had been shown earlier that recombinant Agrin promotes cardiac regeneration after myocardial infarction, the study presented suggests that Polypill-HAAE/HAAV may aid in heart regeneration and repair through induction of Agrin and other genes. And, thereby, it makes those who take Polypill-HAEE/V less susceptible to cardiac dysfunction.

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 of age, by taking Polypill-HAAE/HAAV, they may prevent ageing-associated (or, stress-associated) decline in cardiac function and cardiac dysfunction (fig. 2).

Finally, 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. 4-6).  


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 Polypill-HAAE/HAAV increases the expression of Agrin and promotes cardiac regeneration and repair

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 for Cardioprotection: Polypill-HAAE/HAAV-based therapy for Cardiac repair and myocardial infarction: A four-component  Polypill-HAAE/HAAV consisting of Hydrochlorothiazide (12·5 mg), Aspirin (81 mg), Atorvastatin (20 mg), and Enalapril (5 mg)  or Valsartan (40 mg)  increases Agrin expression, activates Yap and ERK-mediated signaling,  replaces scar tissue with functional cardiomyocytes, and promotes cardiomyocyte regeneration and repair after myocardial infarction, via up-regulation of its target gene, 25/September/2019,  8.45 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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