Methamphetamine-induced cardiotoxicity: in search of protective transcriptional mechanisms.

Abstract

Crystalline methamphetamine hydrochloride is an illegal drug with a high addictive potential, better known by its colloquial name "ice" or "crystal meth". The abuse of this drug has led to significant health problems worldwide. Like other amphetamine-type stimulants, chronic consumption of methamphetamine leads to direct toxic effects on the central nervous system, causing cognitive impairment, depressive behavior, and other severe neurological or psychiatric symptoms. Besides its neurotoxicity, the drug exhibits numerous deleterious effects on the cardiovascular system, including hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, and dilated cardiomyopathy with congestive heart failure and left ventricular dysfunction. The excessive release of catecholamines upon methamphetamine exposure causes vasoconstriction and vasospasm, which ultimately lead to hypertension, tachycardia, endothelial dysfunction, and cardiotoxicity. While numerous studies have focused on transcription factors expressed in the brain that cause the neurotoxic effects of the drug, much less is known about transcription factors involved in the development of methamphetamine-induced heart failure. In this article, we provide an overview of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway involved in ischemia/reperfusion injury in the myocardium, which may be activated by the vasospasm-inducing action of the drug. However, much more work is needed to decipher the precise role of STAT protein family members, including the potentially cardioprotective STAT3, in the pathogenesis of methamphetamine-induced cardiotoxicity.