Introduction: What they say:
A 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 (the number 1 journal in “General science” with an impact factor of 43+), by Prof Tzahor E, Bassat E and others.
A recent study from the Population Health Research Institute, McMaster University and Hamilton Health Sciences, David Braley Research Bldg., Hamilton General Hospital, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada shows that “Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.” This study was published, in the 27 August 2017 issue of the journal “N Engl J Med.” (the number 1 journal in “Clinical medicine” with an impact factor of 72.406), by Dr. Eikelboom, Stuart J. Connolly and others.
What we say:
On the foundation of these interesting findings, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for heart regeneration and repair: A pharmaceutical mixture encompassing Rivaroxaban and Asprin (RA) 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) out of 55 million deaths that occur every year, nearly 18.33 million deaths are due to cardiovascular causes; (3) the raise of death rate, due to cardiovascular disease, has increased from 123 lakhs in 1990 to 173 lakhs in 2013; (4) 85% of people over 80 years are susceptible to cardiovascular diseases;(5) in India, in 2004, 14.6 lakhs deaths (14% of total deaths) were due to ischemic heart disease; (6) the death due to cardiovascular disease is higher in low-to-middle income countries compared to developed countries; (7) the global economic cost spent in the treatment of cardiovascular disease in 2011 was little more than 10 billion US dollars; and (8) an alarming number of people, such as 230 lakhs people, will die from cardiovascular diseases each year from 2030 onwards, 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?
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:
Although Dr. Eikelboom’s research team has shown recently that treating patients with a combination of Rivaroxaban (2.5 mg twice daily) and Asprin (100 mg/day) ameliorates outcome of stable cardiovascular disease than treating them with either drug alone, its mechanism of action is not known.
This study suggests, for the first time, that a pharmaceutical mixture encompassing Rivaroxaban and Asprin (RA), 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 life span (fig 1).
Thus, by treating myocardial patients with a pharmaceutical mixture encompassing Rivaroxaban and Asprin (RA), cardiologists may preserve myocardial function after myocardial infarction; and prevent ageing-associated (or, stress-associated) decline in cardiac function. Together, this study suggests that pharmacological formulations encompassing “Rivaroxaban and Asprin or their analogs, either alone or in combination with any of the known compounds that improve myocardial function,” may be used to heal the damaged cardiac tissue after myocardial infarction.
Figure 1. A pharmaceutical mixture encompassing Rivaroxaban and Asprin functions as a Cardioprotective agent. Mechanistic insights into how Rivaroxaban and Sulforaphane induces the expression of Agrin and other genes that promote cardiac regeneration and repair to prevent myocardial infarction.
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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 a pharmaceutical mixture encompassing Rivaroxaban and Asprin (RA) increases the expression of Agrin and promotes cardiac regeneration and repair
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References:
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Citation: Boominathan, L., Molecular therapy for heart regeneration and repair: A pharmaceutical mixture encompassing Rivaroxaban and Asprin (RA) 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/October/2017, 11.40 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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