Dynorphins in Development and Disease: Implications for Cardiovascular Disease

Abstract

It is well-established that cardiovascular disease continues to represent a growing health problem and significant effort has been made to elucidate the underlying mechanisms. In this review, we report on past and recent high impact publications in the field of intracrine network signaling, focusing specifically on opioids and their interrelation with key modulators of the cardiovascular system and the onset of related disease. We present an overview of studies outlining the scope of cardiovascular and cerebrovascular processes that are affected by opioids, including heart function, ischemia, reperfusion, and blood flow. Specific emphasis is placed on the importance of dynorphin molecules in cerebrovascular and cardiovascular regulation. Evidence suggests that excessive or insufficient dynorphin could make an important contribution to cardiovascular physiology, yet numerous paradoxical observations frequently impede a clear understanding of the role of dynorphin. Thus, we argue that dynorphin-mediated signaling events for which an immediate regulatory effect is disputed should not be dismissed as unimportant, as they may play a role in cross-talk with other signaling networks. Finally, we consider the most recent evidence on the role of dynorphin during cardiovascular-related inflammation and on the potential value of endogenous and exogenous inhibitors of kappa-opioid receptor, a major dynorphin A receptor, to limit or prevent cardiovascular disease and its related sequelae.

The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes

“…Prodynorphin is cleaved to yield dynorphin-B, which has two extended forms (dynorphin-A and dynorphin-B), and leumorphin. In the peripheral circulation, dynorphin-A and dynorphin-B are further cleaved to yield dynorphin A (1-13) (DYN-A(1-13)), dynorphin A (1-8) (DYN-A (1-8)), and dynorphin B (1-13) (DYN-B (1-13)) and rimorphin, respectively [45]. Enkephalins are derived from the precursor protein proenkephalin (PENK) and interact with glutamate and dopamine in the brain reward circuit [46].…”

Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue

“…Dynorphins are mainly expressed in the CNS, especially in the amygdala, entorhinal cortex, dentate gyrus, and nucleus accumbens, where they modulate processes related to learning and memory, emotional control, stress response, and pain [ 29 ]. Moreover, it was reported that myocardial cells express the PDYN gene [ 30 ], underlying the role of dynorphin-B in the control of the cardiovascular system and heart function [ 31 ].…”