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Dr Mandy O J Grootaert

Research Interests

Vascular smooth muscle cells derived from human atherosclerotic plaques show multiple characteristics of senescence, both in vitro and in vivo. Identifying the mechanisms that control this process is crucial to understand their impact on atherogenesis and to develop potentially new anti-atherosclerotic strategies. Sirtuins, a class of enzymes with deacetylase and ADP-ribosyltransferase activity, are expressed in human atherosclerotic plaques and have been implicated in organism longevity, genomic stability, apoptosis, and energy metabolism. Previous work at our laboratory has shown that Sirtuin 1 protects against an unstable atherosclerotic plaque phenotype in mice. Therefore, we investigate their role in vascular smooth muscle cells in regulating DNA damage, senescence, apoptosis and lipid metabolism using different mouse models of atherosclerosis.

Keywords

vascular smooth muscle cells (VSMC) ; apoptosis ; atherosclerosis ; senescence

Collaborators

Key Publications

Autophagy in vascular disease. De Meyer GRY, Grootaert MOJ, Michiels CF, Kurdi A, Schrijvers DM, Martinet W. Circulation Research, 2015 Jan 30;116(3):468-79.

Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherosclerosis. Grootaert MOJ, Da Costa Martins P, Bitsch N, Pintelon I, De Meyer GRY, Martinet W, Schrijvers DM. Autophagy, 2015 Nov;11:2014-2032.

Inhibitor screening and enzymatic activity determination for autophagy target Atg4B using a gel electrophoresis based assay. Cleenewerck M, Grootaert MOJ, Gladysz R, Adriaenssens Y, Roelandt R, Joossens J, Lambeir AM, De Meyer GRY, Declercq W, Augustyns K, Martinet W, Van der Veken P. European Journal of Medicinal Chemistry, 2016 Nov;123:631-638 DOI 10.1016/j.ejmech.2016.07.073.

NecroX-7 reduces necrotic core formation in atherosclerotic plaques of ApoE knockout mice. Grootaert MOJ, Schrijvers DM, Van Spaendonk H, Breynaert A, Hermans N, Van Hoof VO, Nozomi T, Vandenabeele P, Kim SH, De Meyer GRY, Martinet W. Atherosclerosis, 2016 Sep;252:166-174 DOI 10.1016/j.atherosclerosis.2016.06.045.

Caspase-3 deletion promotes necrosis in atherosclerotic plaques of ApoE knockout mice. Grootaert MOJ, Schrijvers DM, Hermans M, De Meyer GRY, Martinet W. Oxidative Medicine and Cellular Longevity, 2016; 2016:3087469.

Long-term depletion of conventional dendritic cells cannot be maintained in an atherosclerotic Zbtb46-DTR mouse model. Rombouts M, Cools N, Grootaert MOJ, de Bakker F, Van Brussel I, Wouters A, De Meyer GRY, De Winter BY, Schrijvers DM. PLoS One, 2017 Jan;12:e0169608 DOI 10.1371/journal.pone.0169608.

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