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Obesity Research
Title
Obesity Research
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iConcept Press
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USD$49.00
ISBN
978-1-922227-67-6
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Chapter 7

Obesity Research

The Role of Dermcidin Isoform 2 in Different Conditions Predisposing to Acute Coronary Syndrome

by Asru Kumar Sinha, Sarbashri Bank, Debipriya Banerjee, Suman Bhattacharya, Pradipta Jana, Rajeshwary Ghosh, Gannareddy V. Girish and Gausal A. Khan

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Abstract

Type I (T1) and Type II (T2) diabetes mellitus (DM) and hypertension are reported to be the major atherosclerotic risk factors leading to acute coronary syndrome (ACS). The identity of the mediator that caused either T1DMB or T2DM that also induce atherosclerosis, was determined to be dermcidin isoform 2 (DCN-2) an environmentally induced stress protein of Mr. 11KDa and was found to cause both T1DMB (environmentally induced diabetes mellitus) and T2DM (insulin resistance diabetes mellitus) that can be produced in mice by injecting 0.15µM and 0.24µM of DCN-2 respectively in the circulation within minutes after the injection; indicating that DCN-2 was not only capable of inducing T1DMB and T2DM but the stress protein was a atherosclerotic risk factor leading to the occurrences of ACS in the both forms of DM. The presence of DCN-2 in the circulation was also found to aggravate the developing ACS to acute myocardial infarction (AMI) due to cardiac cells death in the pericardium. Injection of DCN-2 in rabbit caused the increase of both systolic and diastolic pressure within 60mins. The hypertensive effect of DCN-2 in the animal model indicated the role of DCN-2 in the development of hypertension, a well known risk factor for atherosclerosis. The occurrence of hypercholesterolemia in humans, which is a well known condition for the increased occurrences of ACS for which no mechanistic explanation is currently available, was found to increase the plasma DCN-2 from 50nM to >215nM in hypercholesterolemic subjects suggesting the increase of cholesterol in the circulation was directly related to the increase of plasma DCN-2 levels leading to atherosclerosis, and cholesterol itself was acting like an environmental stress factor for atherosclerosis through the systemic increase of DCN-2. Although the increased occurrence of ACS in breast cancer is well known, no mechanism for ACS in this condition is currently known. It was found that the plasma DCN-2 level in the normal female subjects was 15.50nM which increased to 36.75nM in female breast cancer patients suggesting that the increase of DCN-2 was, an atherosclerotic risk factor, leading to increased occurrences of ACS in breast cancer patients. As DCN-2 was found to be an inhibitor of all known forms of nitric oxide synthase (NOS), the effect of DCN-2 could be neutralized by acetyl salicylic acid (aspirin) an activator of NOS, both in vitro and in subjects with ACS, and also was found to control T1DM, hypertension, hypercholesterolemia including human breast cancer and AMI. In conclusion, it could be suggested that co-morbidity of atherosclerosis that ultimately results in the ACS in various conditions that are considered to be world-wide public health problems including all known forms of diabetes mellitus, hypertension, hypercholesterolemia and breast cancer, was the effect of increased DCN-2 in the circulation which itself might actually cause the conditions that are well known for their pre-disposition to develop ACS, a major killer of human race.

Author Details

Asru Kumar Sinha
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India
Sarbashri Bank
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India; Department of Biochemistry, Vidyasagar University, India
Debipriya Banerjee
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India
Suman Bhattacharya
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India; Department of Biochemistry, Vidyasagar University, India
Pradipta Jana
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India; Department of Biochemistry, Vidyasagar University, India
Rajeshwary Ghosh
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India
Gannareddy V. Girish
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India
Gausal A. Khan
Department of Biochemistry, Sinha Institute of Medical Science and Technology, India

Citation

Asru Kumar Sinha, Sarbashri Bank, Debipriya Banerjee, Suman Bhattacharya, Pradipta Jana, Rajeshwary Ghosh, Gannareddy V. Girish and Gausal A. Khan. The Role of Dermcidin Isoform 2 in Different Conditions Predisposing to Acute Coronary Syndrome. In Obesity Research. ISBN:978-1-922227-67-6. iConcept Press. 2016.

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