Chronic type II diabetes mellitus leads to changes in neuropeptide y receptor expression and distribution in human myocardial tissue

Neuropeptide Y is one of the most abundant neurotransmitters in the myocardium, and is known to influence cardiovascular remodeling. We hypothesized that diabetic neuropathy could possibly be associated with altered neuropeptide Y and its receptor expression levels in myocardium and plasma. Plasma neuropeptide Y levels in diabetic (n = 24, HgbA1c 7.9 ± 1.1%) and non-diabetic (n = 27, HgbA1c 5.8 ± 0.5%) patients undergoing cardiac surgery utilizing cardiopulmonary bypass were analyzed. Right atrial tissue of these patients was used to determine the expression of neuropeptide Y, the receptors 1-5, and leptin by immunoblotting, real-time PCR and immunofluorescence. Apoptosis signaling and endostatin and angiostatin were measured to determine the effects of leptin. Plasma neuropeptide Y levels were significantly increased in patients with Type II diabetes mellitus as compared to non-diabetic patients (P = 0.026). Atrial tissue neuropeptide Y mRNA levels were lower in diabetic patients (P = 0.036). There was a significant up-regulation of myocardial Y ₂ and Y ₅ receptors (P = 0.009, P = 0.01 respectively) in the diabetic patients. Leptin, involved with apoptosis and angiogenesis, was down regulated in diabetic patients (P = 0.05). The levels of caspase-3, endostatin and angiostatin were significantly elevated in diabetic patients (P = 0.003, P = 0.008, P = 0.01 respectively). Y ₁ receptors were more likely to be localized within the nuclei of cardiomyocytes and vascular smooth muscle cells. Neuropeptide expression is altered differentially in the serum and myocardium by diabetes. Altered regulation of this system in diabetics may be in part responsible for the decreased angiogenesis, increased apoptosis, and increased vascular smooth muscle proliferation leading to coronary artery disease and heart failure in this patient population.