Mechanisms of cardiovascular calcification

Our research focus

Mechanisms of cardiovascular calcification

Cardiovascular calcification, which is defined as the pathological calcification of heart valves and arteries, has emerged as a predictor of and contributor to cardiovascular morbidity and mortality. While the association between cardiovascular calcification and cardiovascular events has been established clinically, the molecular mechanisms that control vascular calcification are not well understood. Our research has considerable clinical interest and is an important contribution in advancing our understanding of cardiovascular calcification, particularly in patients with renal failure who have accelerated arterial and valvular calcification. Moreover, emerging evidence suggests that microcalcification may contribute to plaque rupture the leading cause of myocardial infarction.

Our major area of research is the identification of differential mechanisms for cardiovascular calcification and bone remodeling to detect novel therapeutic targets for vascular calcification, which do not negatively impact bone mineralization.

Team

Group leader

Priv.-Doz. Dr. rer. nat. Claudia Goettsch, PhD
Phone: +49 241 80-37312
cgoettschukaachende

Team

Dr. rer. nat. Andrea Gorgels
Postdoc

Regina Lüers
Technische Assistentin

PhD students

Alamgir Alam, MSc

Nicolas Hense, MSc

Anika Himmelsbach, MSc

MD students

Carina Ciliox

Jonas Heyn

Matthias Kampmann

Sophie Schiestel

Joel Simon

Melina Stein

Jan Felix Wolters

All MD and PhD students are part of the cardiorenal graduate school of the SFB219.

We are continuously looking for talented MD and PhD students with an interest in cardiovascular biology. If you are interested please send your CV and a letter of intent to Dr. Goettsch:
cgoettschukaachende

Publications

Selected publications:

Hutchson JD, Goettsch C. Cardiovascular Calcification heterogeneity in chronic kidney disease. Circulation Research. Publikation akzeptiert. DOI: 10.1161/CIRCRESAHA.123.321760
Iqbal F, Schlotter F, Becker-Greene D, Goettsch C, Hutcheson JD, Rogers MA, Halu A, Lee LL, Blaser MC, Mlynarchik A, Hagita S, Kuraoka S, Chen HY, Engert JC, Passos LS, Jha P, Osborn E, Jaffer F, Body, SC, Robson SC, Thanassoulis G, Aikawa M, Singh SA, Sonawana AR, Aikawa E. Sortilin promotes aortic valve disease by enhancing valvular fibrosis and calcification. Eur Heart J 2023;44:885-898.
Heuschkel M, Babler A, Heyn J, van der Vorst E, Steeman M, Gesper M, Kappel B, Magne D, Goueffic Y, Jahnen.Dechent W, Kramann R, Marx N, Quillard T, Goettsch C. Distinct role of mitochondrial function and protein kinase C in intimal and medial calcification in vitro. Manuscript in preparation. Front Cardiovasc Med. 2022;9:959457.
Skenteris NT, Seime T, Witasp A, Karlof E, Wasilewski GB, Heuschkel MA, Jaminon A, Oduor L, Dzhanaev R, Kronqvist M, Lengquist M, Peeters FECM, Sonderberg M, Hultgren R, Roy J, Maegdefessel L, Arnardottir H, Bengtsson E, Goncalves I, Quertermous T, Goettsch C, Stenvinkel P, Schurgers LJ, Matic L. Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification. Clin Transl Med 2022;12:e682
Jankowski V, Saritas T, Kjolby MF, Hermann J, Speer T, Himmelsbach A, Mahr K, Heuschkel M, Schunk SJ, Thirup S, Winther S, Bottcher M, Nyegard M, Nykjaer A, Kramann R, Kaesler N, Jankowski J, Floege J, Marx N, Goettsch C. Carbamylated sortilin associates with cardiovascular calcification in patients with chronic kidney disease. Kidney Int 2022;101:574-584.
Goettsch C, Strzelecka-Kiliszek A, Bessueille L, Quillard, T, Mechtouff L, Pikula S, Canet-Soulas E, Millan JL, Fonta C, Magne D. TNAP as a therapeutic target for cardiovascular calcification - a discussion of its pleiotropic functions in the body. Cardiovasc Res. 2022;118:84-94.
Orth-Alampour S, Gayrard N, Salem S, Bhargava S, Jankowski V, Jover B, Notarnicola C, Noels H, van der Vorst E.P.C., Kuppe C, Wolf M, Goettsch C, Theelen W, Bruck H, Fliser D, Loscalzo J, Wu Z, Marx N, Zidek W, Argiles A, Jankowski J. Prevention of vascular calcification by an endogenous mediator that inhibits osteogenic transdifferentiation. Basic Res Cardiol. 2021;116:57
Heuschkel MA, Skenteris NT, Hutcheson JD, van der Valk DD, Bremer J, Goody P, Hjortnaes J, Jansen F, Bouten CVC, van den Bogaerdt A, Matic L, Marx N, Goettsch C. Integrative Multi-Omics Analysis in Calcific Aortic Valve Disease Reveals a Link to the Formation of Amyloid-Like Deposits. Cells. 2020;9:2164.
Kaesler N, Goettsch C, Weis D, Schurgers L, Hellmann B, Floege J, Kramann R. Magnesium but not nicotinamide prevents vascular calcification in experimental uraemia. Nephrol Dial Transplant. 2019.
Goettsch C, Iwata H, Hutcheson JD, O'Donnell CJ, Chapurlat R, Cook NR, Aikawa M, Szulc P, Aikawa E. Serum Sortilin Associates With Aortic Calcification and Cardiovascular Risk in Men. Arterioscler Thromb Vasc Biol 2017;37:1005-1011.
KramannR, Goettsch C, Wongboonsin J, Iwata H, Schneider RK, Kuppe C, Kaesler N, Chang-Panesso
M, Machado F, Gratwohl S, Vemuri C, Madhurima K, Hutcheson JD, Jain S, Aikawa E, Humphreys EB. Adventitial MSC-like cells are progenitors of vascular smooth muscle cells and drive vascular calcification in chronic kidney disease. Cell Stem Cell2016;19:628-642.
Iwata H, GoettschC, SharmaA, Ricchiuto P, GohWWB, Halu A, Yamada I, Yoshida H, HaraT, Wei M, InoueN, FukudaD, MojcherA, Mattson PC, Barabasi AL, BoothbyN, AikawaE, SinghSA, AikawaM. PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP ribosylation. Nat Commun 2016; 7:12849.
Goettsch C, Hutcheson JD, Hagita S, Rogers M, Pham TH, Creager MD, Jung C, Mlynarchik AK, Kjolby, MF, Aikawa M, Aikawa E. Induction of cardiovascular calcification in non-transgenic mice via a single injection of PCSK9 adeno-associated viral vector. Atherosclerosis 2016;215:109-118.
Goettsch C, Hutcheson JD, Aikawa M, Iwata H, Pham T, Nykjaer A, Kjolby M, Rogers M, Michel T, Shibasaki M, Hagita S, Kramann R, Rader DJ, Libby P, Singh SA, Aikawa E. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles. J Clin Invest 2016; 126:1323-36.
Hutcheson JD, Goettsch C, Bertazzo S, Maldonado N, Ruiz JL, Goh WWB, Yabusaki K, Faits T, Bouten C, Franck G, Quillard T, Libby P, Aikawa M, Weinbaum S, Aikawa E. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. Nat Mater2016;15:335-43.
Goettsch C, BabelovaA, TrummerO, ErbenRE, Rauner M, RammeltS, Weissmann N, Weinberger V, BenkhoffS, KampschulteM, Obermayer-PietschB, HofbauerLC, Brandes RP, Schröder K. NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis. J Clin Invest 2013;123:4731-38.
New SE, Goettsch C, Aikawa M, Marchini JF, Shibasaki M, Yabusaki K, Libby P, Shanahan CM, Croce K, Aikawa, E. Macrophage-Derived Matrix Vesicles: An Alternative Novel Mechanism for Microcalcification in Atherosclerotic Plaques. Circ Res 2013;113:72-7.

For a complete reference list please see PubMed* Link

Funding

German Research Fundation (DFG)
Sonderforschungsbereich Transregio-SFB219 – German Research Fundation (DFG)
- Project C02 and IRTG
ERA-CVD (Federal Ministry of Education and Research, BMBF)
European Union’s Horizon 2020 ITN INTRICARE
German Heart Foundation
Internal funding (START)

Education

Leader of the CardioRenal graduate school of the TRR219
Teaching at the Medical Faculty, RWTH Aachen:
- Co-founder of the Qualifikationsprofil ‚Wissenschafts- und Managementkompetenzen‘ (WMK)‘
- Lecture for ‚How to write a paper‘, ‚How to read a paper‘ and POL
- Lecture: Biomedical engineering