Myocardial Ischemia and Diabetes Mellitus: Role of Oxidative Stress in the Connection between Cardiac Metabolism and Coronary Blood Flow

Abstract

Ischemic heart disease (IHD) has several risk factors, among which diabetes mellitus represents one of the most important. In diabetic patients, the pathophysiology of myocardial ischemia remains unclear yet: some have atherosclerotic plaque which obstructs coronary blood flow, others show myocardial ischemia due to coronary microvascular dysfunction in the absence of plaques in epicardial vessels. In the cross-talk between myocardial metabolism and coronary blood flow (CBF), ion channels have a main role, and, in diabetic patients, they are involved in the pathophysiology of IHD. The exposition to the different cardiovascular risk factors and the ischemic condition determine an imbalance of the redox state, defined as oxidative stress, which shows itself with oxidant accumulation and antioxidant deficiency. In particular, several products of myocardial metabolism, belonging to oxidative stress, may influence ion channel function, altering their capacity to modulate CBF, in response to myocardial metabolism, and predisposing to myocardial ischemia. For this reason, considering the role of oxidative and ion channels in the pathophysiology of myocardial ischemia, it is allowed to consider new therapeutic perspectives in the treatment of IHD.

Figure 1

Pathophysiological basis of IHD and its clinical manifestations.

Figure 2

Pathophysiology of diabetes mellitus and its role in the determinism of IHD.

Figure 3

Role of oxidative stress in the pathogenesis of coronary artery disease and coronary microvascular dysfunction.

Figure 4

Different mechanisms involved in coronary blood flow regulation.

Figure 5

Schematic representation of ion movements through coronary ion channels.

Figure 6

Physiological and pathophysiological roles of H2O2 on voltage-dependent potassium channel (Kv).

Figure 7

An excess of peroxynitrite (ONOO-) may lead to Kv-mediated vasodilatation impairment through Kv1.2 tyrosine residue nitration; 4-hydroxynonenal (4-HNE) targets a cysteine 621 residue of the TRPV1 coronary channel impairing its function and contributing to CMD in diabetes mellitus.