The cardioprotective role of matrix metalloproteinase-2 inhibition in myocardial ischemia/reperfusion injury: preclinical and clinical data
Kiss Krisztina1, Bencsik Péter2,3
1Semmelweis Egyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika, Tűzoltó utcai Részleg, Budapest
2Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Farmakológiai és Farmakoterápiai Intézet, Szeged
3Pharmahungary Csoport, Szeged
Ischemic heart disease, including acute myocardial infarction, currently leads the mortality statistics in Hungary. Over the past nearly four decades, intensive research has been conducted to identify and pharmacologically target cardioprotective processes and molecules against myocardial ischemia/reperfusion injury. Despite this huge effort, there is still no registered drug available that reduces the rate of myocardial infarction. Therefore, the search for new potential drug targets and drug development in this direction is of utmost importance. The role of matrix metalloproteinases (MMPs), particularly MMP-2, in myocardial ischemia/reperfusion injury has been known and intensively studied for more than two decades. Our research group became involved in this field in the early 2000s with the intention of drug development. With the help of a strong Hungarian chemistry background, we have developed several promising drug candidates that have shown reproducible cardioprotection in several preclinical models, but currently, due to the lack of professional chemical support, further experiments have been suspended. The aim of this manuscript is to provide a comprehensive insight, in part, into the basic research background of MMP-2 inhibition toward ischemic cardioprotection, the results of our drug development trials, as well as into the clinical trials available in the international literature.
ISSUE: CARDIOLOGIA HUNGARICA | 2023 | VOLUME 53, ISSUE 5
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