Univ.-Prof. Dr. Donato Santovito

Research areas: atherosclerosis, epigenetics, microRNAs

Donato Santovito is a DZHK Professor for Vascular Immunotherapy at the Ludwig-Maximilians University (LMU) of Munich. His research focuses on epigenetic regulatory mechanisms in cardiovascular disease, with an emphasis on atherosclerosis and its associated immune response.

With his research team, Donato Santovito studies the contribution of epigenetic mechanisms such as non-coding RNAs and histone modifications in atherosclerosis and cardiovascular disease. In particular, his work aims to comprehend canonical and noncanonical functions of microRNAs in cells relevant to cardiovascular disease, elucidate the mechanisms governing their intracellular trafficking and release, explore the intricate interplay of multiple epigenetic regulatory mechanisms, and understand their contributions to vascular (dys)function and communication between stromal and immune cells within and beyond the vessel wall. These investigations combine biophysical and molecular biology methods, sequencing techniques, experiments involving transgenic mouse models in vivo, and ex vivo translational studies. The ultimate goal of his research is to pinpoint molecular mechanisms that could be exploited as therapeutic targets thereby enhancing the standard of care for atherosclerosis andcardiovascular diseases, which still account for the first cause of death worldwide.

• Italian Society of Internal Medicine (SIMI), Research Award in Internal Medicine (2013)

Döring Y, van der Vorst EPC, Yan Y, Neideck C, Blanchet X, Jansen Y, Kemmerich M, Bayasgalan S, Peters LJF, Hristov M, Bidzhekov M, Yin C, Zhang X, Leberzammer J, Li Y, Park I, Kral M, Nitz K, Parma L, Gencer S, Habenicht A, Faussner A, Teupser S, Monaco C, Holdt L, Megens RTA, Atzler D, Santovito D, von Hundelshausen P, Weber C. Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis. Nat Cardiovasc Res. 2024 (in press)

Cimen I, Natarelli L, Kichi ZA, Henderson JM, Farina FM, Briem E, Aslani M, Megens RTA, Jansen Y, Mann-Fallenbuchel E, Gencer S, Duchêne J, Nazari-Jahantigh M, Vorst EPC van der, Enard W, Döring Y, Schober A, Santovito D, Weber C. Targeting a cell-specific microRNA repressor of CXCR4 ameliorates atherosclerosis in mice. Sci Transl Med. 2023;15,adf3357.

Santovito D, Weber C. Non-canonical features of microRNAs: paradigms emerging from cardiovascular disease. Nat Rev Cardiol. 2022;19:620–638.

Mohanta SK, Peng L, Li Y, Lu S, Sun T, Carnevale L, Perrotta M, Ma Z, Förstera B, Stanic K, Zhang C, Zhang X, Szczepaniak P, Bianchini M, Saeed BR, Carnevale R, Hu D, Nosalski R, Pallante F, Beer M, Santovito D, Ertürk A, Mettenleiter TC, Klupp BG, Megens RTA, Steffens S, Pelisek J, Eckstein HH, Kleemann R, Habenicht L, Mallat Z, Michel JB, Bernhagen J, Dichgans M, D’Agostino G, Guzik TJ, Olofsson PS, Yin C, Weber C, Lembo G, Carnevale D, Habenicht AJR. Neuroimmune cardiovascular interfaces control atherosclerosis. Nature. 2022;605:152–159.

Santovito D, Toto L, De Nardis V, Marcantonio P, D’Aloisio R, Mastropasqua A, De Cesare D, Bucci M, Paganelli C, Natarelli L, Weber C, Consoli A, Mastropasqua R, Cipollone F. Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes. Sci Rep. 2021;11:4136.

Santovito D, Egea V, Bidzhekov K, Natarelli L, Mourão A, Blanchet X, Wichapong K, Aslani M, Brunßen C, Horckmans M, Hristov M, Geerlof A, Lutgens E, Daemen M, Hackeng T, Ries C, Chavakis T, Morawietz H, Naumann R, von Hundelshausen P, Steffens S, Duchêne J, Megens RTA, Sattler M, Weber C. Non-canonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis. Sci Transl Med. 2020;12:eaaz2294.

Santovito D, Marcantonio P, Mastroiacovo D, Natarelli L, Mandolini C, Nardis V, Paganelli C, De Cesare D, Affaitati G, Giamberardino M, Stellin L, Pinelli M, Weber C, Blasis G, Occhiuzzi U, Bucci M, Desideri G, Cipollone F. High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion. Int J Cardiol. 2020;299,249-253.

Bianchini M, Duchêne J, Santovito D, Schloss MJ, Evrard M, Winkels H, Aslani M, Mohanta SK, Horckmans M, Blanchet X, Lacy M, von Hundelshausen P, Atzler D, Habenicht A, Gerdes N, Pelisek J, Ng LG, Steffens S, Weber C, Megens RTA. PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function. Sci Immunol. 2019;4:eaar3054.

Horckmans M, Bianchini M, Santovito D, Megens RTA, Springael J-Y, Negri I, Vacca M, Di Eusanio M, Moschetta A, Weber C, Duchene J, Steffens S. Pericardial adipose tissue regulates granulopoiesis, fibrosis, and cardiac function after myocardial infarction. Circulation. 2018;137:948–960.

Santovito D, De Nardis V, Marcantonio P, Mandolini C, Paganelli C, Vitale E, Buttitta F, Bucci M, Mezzetti A, Consoli A, Cipollone F. Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: effect of glycemic control. J Clin Endocrinol Metab. 2014;99:E1681–5.

Atherosclerosis: RNA fragment creates prospect for new therapies

How a microRNA protects vascular integrity

Heilung nach Herzinfarkt: woher die Immunantwort kommt