The Role of Dermcidin Isoform 2: A Two-Faceted Atherosclerotic Risk Factor for Coronary Artery Disease and the Effect of Acetyl Salicylic Acid on It

Abstract

Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 μM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.

An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction

“…Insulin can activate nitric oxide synthase and inhibit platelet aggregation and thus produce a beneficial effect on cardiovascular disease 29 . Aspirin can further increase plasma insulin levels by decreasing plasma dermcidin levels and reducing the infarct size in patients with AMI 27 30 . Our finding of that admission hyperglycemia was statistical significantly associated with the development of MACEs only in patients with HbA1c ≤ 7% further supported the hypothesis that SIH would worsen the prognosis.…”

Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

“…In animal models, dermcidin has been shown to induce platelet aggregation and coronary artery disease by activating platelet cyclooxygenase and inhibiting the constitutive form of nitric oxide synthase, respectively, with an efficiency 40 times higher than that of ADP at activating cyclooxygenase. 182 Notably, dermcidin was able to stimulate the development of coronary artery disease in one animal model, even at suboptimal concentrations of ADP within 30 min. 183 Together, these observations suggest that the ability of AMPs to fight infections depends on their induction by infectious microorganisms, the particular peptides generated, and the local environment/tissue in which they act.…”

“…Dermcidin isoform 2 is known as a stress-induced oxidative protein capable of inhibiting the synthesis of nitric oxide in endothelial cells, insulin in pancreatic islet β-cells, and hepatic hormone synthesis. 182 Also, hypertensive patients show significantly higher levels of plasma dermcidin, but salicylic acid has been shown to reduce dermcidin levels while simultaneously attenuating dermcidin-mediated insulin inhibition in patients with acute myocardial infarction. 183 Therefore, the exploitation of dermcidin isoform 2 for antimicrobial therapeutic purposes is most likely not possible due to severe side effects.…”

Neutralization by Insulin of the Hypertensive Effect of Dermcidin Isoform 2: An Environmentally Induced Diabetogenic and Hypertensive Protein

“…Although no reports are available on the effects of environmental stresses on animals, particularly because the environmental stresses might not produce any effect in animals unlike in the case of human beings due to species differences, our results as described under Figure 1 suggested that these well-known stresses were capable of increasing dermcidin, which is reported to be a causative agent for both diabetes mellitus and hypertension [7]. We have also found that hypoxia, pure nicotine, and tobacco leaf extract were capable of expressing dermcidin gene within 30 mins of incubation in tissue culture of muscle cells, liver cells (primary culture), and endothelial cells of mice (unpublished) and also in the plasma of human volunteers exposed to hypoxia due to high altitude [26].…”