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Atherosclerosis is a major cause of a huge variety of disease entities and has been in the focus of medical and biochemical research for many decades. Therefore, we aim to identify mechanisms that are involved in the development and progression of coronary artery disease (CAD). A main focus of our research work is on epicardial adipose tissue (EAT) that secretes proinflammatory and proatheroslcerotic cytokines and thus, might play a major role in the formation of atherosclerotic CAD plaques. Recent studies could proof a positive correlation between the amount of EAT and the extent and the severity of coronary artery calcium score.
The clinical relevance of myocardial perfusion deficits as the earliest manifestation of CAD is studied with high temporal and spatial resolution in cooperation with Institute of Clinical Radiology and Nuclear Medicine (Prof. Dr. med. S.0. Schönberg).
On the molecular level, platelet-endothelial cell interactions play an important role in the initiation and acceleration of atherosclerosis. We developed an in vitro platelet-endothelial cell model to study the well-established cell-surface markers ICAM-1, VCAM-1, uPAR, MT1-MMP on endothelial cells and CD62P and CD40L on platelets and to examine the atheroprotective potential of new therapeutic tools for cardiovascular disease.
The research work of our group in the field of vascular biology and medicine aims to
- to investigate the relevance of functional, morphological and clinical parameters on the extent of the amount of EAT in patients with CAD.
- to identify influencing factors on the longitudinal course of EAT mass and to study changes of EAT over time in patients with CAD.
- to establish new diagnostic tools to detect hemodynamically relevant stenosis in comparison to standard examination procedures and to evaluate their potential clinical benefit in daily clinical practice.
- to perform an accurate plaque characterization with cardiac CT, PET-CT and optical coherence tomography to identify new markers for plaque progression and to improve risk stratification.
- to explore mechanisms of platelet-endothelial cell interaction, to gain insight into their involvement in the atherosclerotic process and to detect new therapeutic targets.
- Doesch C, Dierks DM, Haghi D, Schimpf R, Kuschyk J, Suselbeck T, Schoenberg SO, Borggrefe M, Papavassiliu T: Right ventricular dysfunction, late gadolinium enhancement, and female gender predict poor outcome in patients with dilated cardiomyopathy. Int J Cardiol. 177:429-435, 2014.
- Hu D, Barajas-Martínez H, Pfeiffer R, Dezi F, Pfeiffer J, Buch T, Betzenhauser MJ, Belardinelli L, Kahlig KM, Rajamani S, DeAntonio HJ, Myerburg RJ, Ito H, Deshmukh P, Marieb M, Nam GB, Bhatia A, Hasdemir C, Haïssaguerre M, Veltmann C, Schimpf R, Borggrefe M, Viskin S, Antzelevitch C:Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol. 64:66-79, 2014.
- Tülümen E, Giustetto C, Wolpert C, Maury P, Anttonen O, Probst V, Blanc JJ, Sbragia P, Scrocco C, Rudic B, Veltmann C, Sun Y, Gaita F, Antzelevitch C, Borggrefe M, Schimpf R: PQ segment depression in patients with short QT syndrome: a novel marker for diagnosing short QT syndrome? Heart Rhythm. 11:1024-1030, 2014.
- Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, Verkerk AO, Schwartz PJ, Crotti L, Dagradi F, Guicheney P, Fressart V, Leenhardt A, Antzelevitch C, Bartkowiak S, Borggrefe M, Schimpf R, Schulze-Bahr E, Zumhagen S, Behr ER, Bastiaenen R, Tfelt-Hansen J, Olesen MS, Kääb S, Beckmann BM, Weeke P, Watanabe H, Endo N, Minamino T, Horie M, Ohno S, Hasegawa K, Makita N, Nogami A, Shimizu W, Aiba T, Froguel P, Balkau B, Lantieri O, Torchio M, Wiese C, Weber D, Wolswinkel R, Coronel R, Boukens BJ, Bézieau S, Charpentier E, Chatel S, Despres A, Gros F, Kyndt F, Lecointe S, Lindenbaum P, Portero V, Violleau J, Gessler M, Tan HL, Roden DM, Christoffels VM, Le Marec H, Wilde AA, Probst V, Schott JJ, Dina C, Redon R: Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nat Genet. 45:1044-1049, 2013.
- Doesch C, Papavassiliu T, Michaely HJ, Attenberger UI, Glielmi C, Süselbeck T, Fink C, Borggrefe M, Schoenberg SO: Detection of myocardial ischemia by automated, motion-corrected, color-encoded perfusion maps compared with visual analysis of adenosine stress cardiovascular magnetic resonance imaging at 3 T: a pilot study. Invest Radiol. 48:678-686, 2013.
- Doesch C, Süselbeck T, Haghi D, Streitner F, Schoenberg SO, Borggrefe M, Papavassiliu T. The relationship between the severity of coronary artery disease and epicardial adipose tissue depends on the left ventricular function. PLoS One. 7:e48330, 2012.
- Streitner I, Goldhofer M, Cho S, Kinscherf R, Thielecke H, Borggrefe M, Süselbeck T, Streitner F: Cellular imaging of human atherosclerotic lesions by intravascular electric impedance spectroscopy. PLoS One. 7:e35405, 2012.
- Giustetto C*, Schimpf R*, Mazzanti A, Scrocco C, Maury P, Anttonen O, Probst V, Blanc JJ, Sbragia P, Dalmasso P, Borggrefe M, Gaita F: Long-Term Follow-Up of Patients With Short QT Syndrome. J Am Coll Cardiol. 58:587–595, 2011.
- 10. Stach K, Kälsch AI, Nguyen XD, Elmas E, Kralev S, Lang S, Weiss C, Borggrefe M, Kälsch T. 1a,25-dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells. Cardiology. 118:107-15, 2011.
- Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, Babuty D, Sacher F, Borggrefe M, Haissaguerre M, Mabo P, Le Marec H, Wolpert C, Wilde AAM: Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada registry. Circulation. 121: 635-643, 2010.
Prof. Dr. Martin Borggrefe
1st Department of Medicine, Cardiology
affiliated at the DZHK (German Centre for Cardiovascular Research)
University Medical Centre Mannheim
Medical Faculty Mannheim
Theodor-Kutzer Ufer 1-3
Phone +49 621/383-2204