Pre- and Post-Conditioning of the Heart: An Overview of Cardioprotective Signaling Pathways

Abstract

: Since the discovery of ischemic pre- and post-conditioning, more than 30 years ago, the knowledge about the mechanisms and signaling pathways involved in these processes has significantly increased. In clinical practice, on the other hand, such advancement has yet to be seen. This article provides an overview of ischemic pre-, post-, remote, and pharmacological conditioning related to the heart. In addition, we reviewed the cardioprotective signaling pathways and therapeutic agents involved in the above-mentioned processes, aiming to provide a comprehensive evaluation of the advancements in the field. The advancements made over the last decades cannot be ignored and with the exponential growth in techniques and applications. The future of pre- and post-conditioning is promising.

Angiotensin 1–7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart—The signaling mechanism

“…Understanding the molecular mechanism of the infarctlimiting effect of angiotensin 1-7 depends on the answer to this question. It has been found that receptors providing cardiac tolerance to I/R (opioid, cannabinoid, bradykinin, and adenosine) are associated with G i/o -, G q -, and G 11 -proteins [23][24][25]. There is evidence suggesting that the Mas receptor is coupled to G 11protein [20].…”

“…It is reported that intravenous administration of angiotensin 1-7 (8 pmol/kg = 7.2 μg/kg) to rats promotes stimulation of JAK2, Akt, and PI3K in the rat myocardium [96]. These kinases provide cardiac tolerance to I/R [23]. Stimulation of Akt and PI3K occurs due to the activation of the Mas receptor, and the stimulation of JAK2 occurs due to the activation of the AT 1 receptor.…”

“…Reactive oxygen species (ROS) are involved in reperfusion cardiac injury [41]. However, ROS are intracellular messengers, which are involved in the cardioprotective effect of ischemic pre‐ and postconditioning [23]. Angiotensin 1–7 (10 μmol/L) stimulated superoxide radical (O 2 • ) production by endothelial cells in vitro [48].…”

KATP channels are regulators of programmed cell death and targets for the creation of novel drugs against ischemia/reperfusion cardiac injury

“…Apoptosis is also involved in death of cardiomyocytes during I/R of the heart [116,117]. Diazoxide and pinacidil inhibited apoptosis induced by oxidative stress in neonatal rat cardiomyocytes by H 2 O 2 [118].…”

“…Rupture of the cell membrane is observed not only at necrosis but also at pyroptosis [127,128], necroptosis [129,130], and ferroptosis [130]. There is evidence that pyroptosis and necroptosis are involved in I/R cardiac injury [117,127,131]. It could be hypothesized that the cardioprotective effect of KCOs could be mediated not only via inhibition of necrosis but also by inhibition of pyroptosis and necroptosis.…”