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المؤلفEl-Yazbi, Ahmed F.
المؤلفElrewiny, Mohamed A.
المؤلفHabib, Hosam M.
المؤلفEid, Ali H.
المؤلفElzahhar, Perihan A.
المؤلفBelal, Ahmed S.F.
تاريخ الإتاحة2023-12-28T05:14:42Z
تاريخ النشر2023
اسم المنشورMolecular Pharmacology
المصدرScopus
الرقم المعياري الدولي للكتاب0026895X
معرّف المصادر الموحدhttp://dx.doi.org/10.1124/molpharm.123.000704
معرّف المصادر الموحدhttp://hdl.handle.net/10576/50639
الملخصCardiovascular complications of diabetes and obesity remain a major cause for morbidity and mortality worldwide. Despite significant advances in the pharmacotherapy of metabolic disease, the available approaches do not prevent or slow the progression of complications. Moreover, a majority of patients present with significant vascular involvement at early stages of dysfunction prior to overt metabolic changes. The lack of disease-modifying therapies affects millions of patients globally, causing a massive economic burden due to these complications. Significantly, adipose tissue inflammation was implicated in the pathogenesis ofmetabolic syndrome, diabetes, and obesity. Specifically, perivascular adipose tissue (PVAT) and perirenal adipose tissue (PRAT) depots influence cardiovascular and renal structure and function. Accumulating evidence implicates localized PVAT/PRAT inflammation as the earliest response tometabolic impairment leading to cardiorenal dysfunction. Increasedmitochondrial uncoupling protein 1 (UCP1) expression and function lead to PVAT/PRAT hypoxia and inflammation as well as vascular, cardiac, and renal dysfunction. As UCP1 function remains an undruggable target so far, modulation of the augmented UCP1-mediated PVAT/PRAT thermogenesis constitutes a lucrative target for drug development to mitigate early cardiorenal involvement. This can be achieved either by subtle targeted reduction in UCP-1 expression using innovative proteolysis activating chimericmolecules (PROTACs) or by supplementation with cyclocreatine phosphate, which augments the mitochondrial futile creatine cycling and thus decreases UCP1 activity, enhances the efficiency of oxygen use, and reduces hypoxia. Once developed, thesemolecules will be first-in-class therapeutic tools to directly interferewith and reverse the earliest pathology underlying cardiac, vascular, and renal dysfunction accompanying the earlymetabolic deterioration.
راعي المشروعThis work is supported by [Grant 45912] (to A.F.E.-Y.) from the Science, Technology, and Innovation Funding Authority in Egypt. No author has an actual or perceived conflict of interest with the contents of this article. Primary laboratory of origin: Research and Innovation Hub, Alamein International University (Alamein, Egypt). dx.doi.org/10.1124/molpharm.123.000704.
اللغةen
الناشرAmerican Society for Pharmacology and Experimental Therapy (ASPET)
الموضوعThermogenic Modulation of Adipose Depots
Cardiovascular complications of diabetes
Early Cardiorenal Complications
Metabolic Impairment
العنوانThermogenic Modulation of Adipose Depots: A Perspective on Possible Therapeutic Intervention with Early Cardiorenal Complications of Metabolic Impairment
النوعArticle
الصفحات187-194
رقم العدد5
رقم المجلد104
dc.accessType Abstract Only


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