Stem Cell Research that Might Lead to Prevention and Treatment of Heart Failure
BRG1 promotes production of a protein that leads to heart failure (photo from Clayman, R. ed. "Your Heart")
To prevent and control heart failure
Heart failure results from lack of oxygen in several organs owing to inability of the heart to pump enough blood (D’ Alonzo, C.A., M.D. A Handbook of Heart Disease, Blood Pressure and Strokes. 1962).
“An inability of the heart to deliver sufficient blood to meet the metabolic requirements of the body in the presence of an adequate intracardia filing pressure is the essential pathophysiological basis for heart failure.
“Roughly 40% of all patients with heart failure have a history of both hypertension and ischaemic heart disease, and about 20% have an antecedent history of diabetes mellitus” (Swaraj, K. MBBS, et al. Chronic Heart Failure: Pathophysiology and Patient Assessment. Medical Progress. 2005. Nov.).
These are the common views of heart failure.
New view of heart failure
There is now an explanation of heart failure linked to the heredity materials DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).
Given a person who is stressed owing to hypertension, or angina. A hitherto dormant molecule, a RNA, is activated and modifies some codes in the DNA of the same person. This RNA is a long non-coding component of the heredity material. DNA has the information code that is transmitted through RNA for the manufacture of proteins, like heart muscle. But this RNA is suppressed, presumably no longer needed, when the heart of the fetus could proceed in its development.
Modification of DNA results in heart failure
This was found by a research team, led by Ching-Pin Chang, M.D., Ph.D., associate professor of medicine at the Indiana University School of Medicine (Bioscience. Newly Discovered Heart Molecule Could Lead to Effective Treatment for Heart Failure. Internet. Aug. 12,2014). The research results were published in Nature in 2010.
The RNA is called “Myheart—for myosin heavy-chain-associated RNA transcript....”. Myheart controls the production of a protein called BRG1. During a stressful situation the production of Myheart is suppressed —when it is most needed. Myheart is supposed to suppress the production of BRG1. Unopposed BRG1 latches on DNA modifying its code. Result: heart failure. Modification may consist of rearrangement of amino acids, like AGCT to GATC. Such change in sequence results in the production of a different protein. A means adenine; G means guanine; C means cytosine; T means tyrosine.
The experiment of Chang and his team was done on mice.
“...They were able to restore Myheart to normal levels using gene transfer technology. Restoring Myheart levels blocked BRG1 actions and prevented heart failure....” (same source as above).
The same procedure can be tried on humans to prevent or treat heart failure. However, Myheart is very large to be delivered as a drug, Dr. Chang said.
The research team is now looking for a subsection of Myheart that can work the way the whole molecule works.
Stem cell research
That Myheart is suppressed during the development of the fetus points to stem cells.
To recall, one stem cell develops into a whole human being. The zygote, union of the male’s sperm and female’s egg, develops into an embryo, that develops into a fetus. This development involves differentiation. (I have a Hub “How One Stem Cell Develops into A Human Being”). During differentiation, production of Myheart is suppressed in the second or later stage. The stages of differentiation are totipotent stem cell (zygote), pluripotent stem cell, multipotent stem cell, unipotent stem cell; adult stem cell; and adult cell - in that order of irreversible development. An adult human being consists of adult cells and reserves of stem cells.
An adult cell, like skin, can now be reprogrammed to produce pluripotent stem cells, called induced pluripotent stem cells (iPS). iPS differentiate and develop into adult cell.(So far no adult human being has been developed in a test tube). This was discovered by Shinya Yamanaka, co-winner with John Gurdon of the Nobel Prize in medicine. So instead of gene transfer involving biotechnology, reprogrammed skin cells can be used. The objective is to produce a normal level of Myheart in a person who is highly stressed. A normal level of Myheart would prevent the production of BRG1.
“Reprogrammed skin cells produces a normal level of Myheart in an adult person.”
The prediction in this hypothesis is that reprogrammed skin cells will produce a normal level of Myheart.
A research in stem cell will verify if indeed reprogrammed skin cells produce a normal level of Myheart in a highly stressed person.
Once the hypothesis is verified true, the hypothesis will turn into a theory. This theory will serve as a guide in the prevention of heart failure. It will also serve as a guide in the treatment of heart failure. The procedure is called stem cell therapy.
Reprogramming of skin cells overrides the need for a large Myheart molecule. It is difficult to deliver a large molecule in a human being.
It is similar to the difficulty in the delivery of glutathione in a human being. Glutathione is a large molecule consisting of three peptides. When ingested, glutathione is broken down by the acids of the stomach into three peptides when some losses in ingredients occur. Then assembled into glutathione inside the body - less potent than the potential one (Pressman, Allan and Sheila S. Buff. Glutathione: the Ultimate Antioxidant. 1998). Glutathione makes three enzymes built-in in the body that neutralize the master free radical, superoxide.
To override the delivery of glutathione as tripeptide, components are delivered instead. For one, this is done by the consumption of plant part or juice that contains ingredients of glutathione. The ingredients are glutamate, glycine, cysteine and co-factors selenium, zinc, lipoic acid and vitamin B2. The juice or fruit or capsule of noni (Morinda citrifolia Linn.) contains these ingredients (Fontanilla. C.D. Benefits Derived from PhilNONI.2008).
There is a speculation that accompanies the hypothesis mentioned above.
The natural suppression of Myheart during the development of the fetus will not occur in the same person given stem cell therapy. Differentiation also consists of activation and suppression of the expression of genes. Stem cell therapy is speculated to override natural suppression of the RNA Myheart. Myheart suppresses the production of BRG1 resulting in prevention or treatment of heart failure.
Copyright Conrado D. Fontanilla. 2014