THE RELATIONSHIP BETWEEN THE EXPRESSION LEVELS OF TISSUE INHIBITOR OF METALLOPROTEINASES-3 (TIMP3) AND SEVERITY OF ATHEROSCLEROSIS

Year 2021, Volume: 84 Issue: 4, 472 - 481, 01.10.2021

Gizem Çelebi , Filiz Güçlü Geyik Emine Dilek Yılmazbayhan , Deniz Özsoy Cenk Eray Yıldız Mustafa Yıldız , Doğaç Öksen Mehmet Cavlak , Evrim Komurcu-bayrak

https://doi.org/10.26650/IUITFD.2021.896230

Abstract

Objective: Tissue Inhibitor of Metalloproteinase-3 human (TIMP3) is one of tissue inhibitors of metalloproteinases (TIMPs), which binds to the components of the extracellular matrix, and has crucial roles in atherosclerogenesis and adipose tissue differentiation. In this study, it was aimed to determine the effects of TIMP3 gene expression levels on severity of atherosclerosis in different tissues. Material and Methods: The first group of the study (evaluated for coronary artery disease) were cases classified as high and low plaque scores according to the degree and location of atherosclerotic lesions. In the second group (post-mortem cases) were male cadavers who died due to coronary heart disease (CHD, n=26) and non-cardiac trauma (T-nonP, n=4). The TIMP3 expression levels were examined in leukocyte and peri-coronary epicardial adipose tissues (EAT) samples (n=69 and n=34, respectively) of the first group and EAT and coronary artery samples (n=12 and n=30, respectively) of the second group using quantitative RT-PCR. In addition, the protein expressions of TIMP3 were analysed on artery sections by immunofluorestaining. Results: In the post-mortem study group, the TIMP3 expression levels were found to increase in no plaque segments of arteries of cases with CHD (CHD-nonP) compared to advanced atherosclerotic arteries (CHD-P) and normal arteries of T-nonP cases (p=0.01 and p=0.05, respectively). The TIMP3 expressions in EATs and leukocytes were not statistically significant between the study groups. In addition, TIMP3 protein was detected in normal arteries, peri-coronary EATs and mostly in macrophages- rich areas in advanced atherosclerotic arteries. Conclusion: Tissue Inhibitor of Metalloproteinase-3 human (TIMP3) expression levels increase in normal coronary arterial segments of cases with CHD, which depict a protective role of TIMP3 in development of atherosclerosis.

Keywords

Atherosclerosis, TIMP3, gene expression level, coronary artery, adipocyte, leukocyte

Supporting Institution

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

TSA-2016-21496 ve 28473

Thanks

We are grateful to Dr. Sema Bilgic for her contribution in the application of cryosection method.

METALLOPROTEİNAZ-3 DOKU İNHİBİTÖRÜNÜN (TIMP3) İFADE DÜZEYLERİ İLE ATEROSKLEROZUN ŞİDDETİ ARASINDAKİ İLİŞKİ

Abstract

Amaç: Hücre dışı matriksin bileşenlerine bağlanan TIMP3, metaloproteinazların doku inhibitörlerinden (TIMP’ler) biridir ve ateroskleroz gelişimi ile yağ dokusu farklılaşmasında rol oynamaktadır. Bu çalışmada, farklı dokulardaki TIMP3 gen ifade düzeylerinin ateroskleroz şiddeti üzerine olan etkisinin belirlenmesi amaçlandı. Gereç ve Yöntemler: Çalışmanın ilk grubu (koroner arter hastalığı için değerlendirilen), aterosklerotik lezyonların derecesine ve yerine göre yüksek ve düşük plak skoru olarak sınıflandırılan vakalardı. İkinci grup (post-mortem vakalar), koroner kalp hastalığı (CHD, n=26) ve kardiyak olmayan travma (T-nonP, n=4) nedeniyle ölen erkek kadavralardı. Birinci grubun lökosit ve peri-koroner epikardiyal yağ doku (EYD) örnekleri (sırasıyla, n=69 ve n=34) ile ikinci grubun EYD ve koroner arter örneklerinde (sırasıyla, n=12 ve n=30) TIPM3 ifade düzeyleri kantitatif RT-PCR ile incelendi. Ek olarak, TIMP3 protein lokalizasyonları, immunfluoresans tekniği ile belirlendi. Bulgular: Post-mortem çalışma grubunda, TIMP3 ifade düzeylerinin CHD’li vakaların plaksız arter segmentlerinde (CHD-nonP), ileri aterosklerotik arterlere (CHD-P) ve T-nonP vakaların normal arterlere kıyasla arttığı bulundu (sırasıyla, p=0.01 ve p=0.05). Lökosit ve EYD’lerdeki TIMP3 gen ifadeleri, çalışma grupları arasında istatistiksel olarak anlamlı fark göstermedi. Ek olarak, TIMP3 proteini normal arter, peri-koroner EYD ve ileri aterosklerotik arterde makrofajların yoğun olduğu alanlarda tespit edildi. Sonuç: CHD’li vakaların normal koroner arteriyel segmentlerinde TIMP3 ifadesindeki artışın ateroskleroz gelişimine karşı koruyucu bir etkisi olabileceğini göstermektedir

Keywords

Ateroskleroz, TIMP3, gen ifade seviyesi, koroner arter, adiposit, lökosit

Project Number

TSA-2016-21496 ve 28473

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