A key to certain lifestyle diseases

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Wednesday, August 21, 2013

A TURKISH proverb goes: “A small key opens big doors.”

Collins online dictionary identifies heart disease, stroke, obesity, and osteoporosis as part of its definition of “lifestyle disease.” Wikipedia includes more—Alzheimer’s disease, atherosclerosis, asthma, certain kinds of cancer, cirrhosis, chronic obstructive pulmonary disease, Type 2 diabetes, metabolic syndrome, chronic renal failure and depression.

Three of the most closely connected diseases—heart disease, obesity and Type 2 diabetes—apparently share a common turnkey that opens the door to their development in a person. Six researchers from Scott & White Memorial Hospital and Clinic in Temple, Texas, identified it as Serpine 1, a variant form of the gene that encodes the precursor substance that later gives rise to the hormone angiotensin. Angiotensin causes the constriction of blood vessels as a mechanism of regulating blood pressure.


Serpine 1, or Serpine Peptidase Inhibitor Clade E, can be found in the extracellular spaces (spaces outside the body cells).

In a study published in the Journal of Proteomics Bioinformation (June 2010), lead
researcher Punit Kaur of the Department of Pathology and his team noted Serpine 1 is “the key protein found and associated in the network of pathways involved in disease generation for obesity, diabetes and cardiovascular diseases.” This happens when the angiotensin precursor gene mutates into the variant gene.

Normally, when the angiotensin precursor reacts with angiotensinogen precursor, it forms the angiotensin I that, in the presence of angiotensin converting enzyme, generates the physiologically active enzyme called angiotensin II. Angiotensin II is the hormone that maintains normal blood pressure.

Proteins like fibrin (blood clot) and precursor Rhodopseudominas A1, and transcription regular genes such as Forkhead Box D1, can directly activate Serpine 1. Enzymes like peptidases and fibronectin 1 can only indirectly activate the mutant gene.

In response, drug companies formulated drugs that can inhibit Serpine 1 activity in order to help manage obesity, hypertension, and diabetes. The Kaur study noted direct inhibitory effect of drotrecogin alfa (anti-obesity) on Serpine 1. Indirect effects had been noted from Eprosartan (anti-obesity, antihypertensive, antidiabetic); Premarin (anti-obesity, antihypertensive); and Ramipril (anti-obesity, antihypertensive). An experimental drug called MCL-9042 had also indirect action on Serpine 1.

William Arthur Ward, author of Fountains of Faith (1970), wrote: “Three keys to more abundant living: caring about others, daring for others, sharing with others.”


Published in the Sun.Star Cebu newspaper on August 21, 2013.


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