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      Smoking, alcohol and opioids effect on coronary microcirculation: an update overview

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          Abstract

          Smoking, heavy alcohol drinking and drug abuse are detrimental lifestyle factors leading to loss of million years of healthy life annually. One of the major health complications caused by these substances is the development of cardiovascular diseases (CVD), which accounts for a significant proportion of substance-induced death. Smoking and excessive alcohol consumption are related to the higher risk of acute myocardial infarction. Similarly, opioid addiction, as one of the most commonly used substances worldwide, is associated with cardiac events such as ischemia and myocardial infarction (MI). As supported by many studies, coronary artery disease (CAD) is considered as a major cause for substance-induced cardiac events. Nonetheless, over the last three decades, a growing body of evidence indicates that a significant proportion of substance-induced cardiac ischemia or MI cases, do not manifest any signs of CAD. In the absence of CAD, the coronary microvascular dysfunction is believed to be the main underlying reason for CVD. To date, comprehensive literature reviews have been published on the clinicopathology of CAD caused by smoking and opioids, as well as macrovascular pathological features of the alcoholic cardiomyopathy. However, to the best of our knowledge there is no review article about the impact of these substances on the coronary microvascular network. Therefore, the present review will focus on the current understanding of the pathophysiological alterations in the coronary microcirculation triggered by smoking, alcohol and opioids.

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          Most cited references186

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          Myocardial ischemia-reperfusion injury: a neglected therapeutic target.

          Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.
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              Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions.

              Hypoxia-inducible factor (HIF-1) is an oxygen-dependent transcriptional activator, which plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and one of three subunits (HIF-1alpha, HIF-2alpha or HIF-3alpha). The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, and phosphorylation. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, and p300/CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)- mediated ubiquitin-proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, in the hypoxia condition, HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation/survival, and glucose/iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1a itself or HIF-1alpha interacting proteins inhibit tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. This review summarizes the molecular mechanism of HIF-1a stability, the biological functions of HIF-1 and its potential applications of cancer therapies.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                BMC Cardiovascular Disorders
                BMC Cardiovasc Disord
                Springer Science and Business Media LLC
                1471-2261
                December 2021
                April 15 2021
                December 2021
                : 21
                : 1
                Article
                10.1186/s12872-021-01990-y
                f473fd40-d33a-41ff-8118-7c0ee2680052
                © 2021

                http://creativecommons.org/licenses/by/4.0/

                http://creativecommons.org/licenses/by/4.0/

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