{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:49:47Z","timestamp":1791614987198,"version":"4.3.4"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,3,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Arterial hypertension and its organ sequelae show characteristics of T cell\u2013mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1\u03b2 demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout\u2013deficient mice received propionate (200 mmol\/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg\u00b7kg\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b7d\n                      <jats:sup>\u20131<\/jats:sup>\n                      subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg\u00b7kg\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b7d\n                      <jats:sup>\u20131<\/jats:sup>\n                      subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II\u2013infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout\u2013deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell\u2013depleted angiotensin II\u2013infused mice, suggesting the effect is regulatory T cell\u2013dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.118.036652","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T08:44:06Z","timestamp":1547714646000},"page":"1407-1421","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":777,"title":["Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage"],"prefix":"10.1161","volume":"139","author":[{"given":"Hendrik","family":"Bartolomaeus","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Balogh","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Yakoub","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, Germany (M.Y., S. H\u00f6ges, L.H., L.C.R., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Homann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, University Hospital, Universit\u00e4tsrat, D\u00fcsseldorf, Germany (S. Homann, M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lajos","family":"Mark\u00f3","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"H\u00f6ges","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, Germany (M.Y., S. H\u00f6ges, L.H., L.C.R., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Tsvetkov","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics and Interfaculty Center of Pharmacogenomics and Drug Research, T\u00fcbingen, Germany (D.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Krannich","sequence":"additional","affiliation":[{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Wundersitz","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen G.","family":"Avery","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Haase","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Kr\u00e4ker","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Hering","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, Germany (M.Y., S. H\u00f6ges, L.H., L.C.R., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Maase","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University of M\u00fcnster, Germany (M.M., K.K.-V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kusche-Vihrog","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University of M\u00fcnster, Germany (M.M., K.K.-V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Grandoch","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacology, University Hospital, Universit\u00e4tsrat, D\u00fcsseldorf, Germany (S. Homann, M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Fielitz","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Greifswald (J.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kempa","sequence":"additional","affiliation":[{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"Integrative Proteomics and Metabolomics Platform, Berlin Institute for Medical Systems Biology, Germany (S. Kempa)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Gollasch","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (M.G., K.-U.E., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaxybay","family":"Zhumadilov","sequence":"additional","affiliation":[{"name":"National Laboratory Astana Nazarbayev University, Kazakhstan (Z.Z., S. Kozhakhmetov, A. 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Kushugalova)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Uwe","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (M.G., K.-U.E., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin (H.B., A.B., L.M., S.W., E.G.A., N.H., K.K., J.F., R.D., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Christian","family":"Rump","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, Germany (M.Y., S. H\u00f6ges, L.H., L.C.R., J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia K.","family":"Forslund","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. Krannich, E.G.A., N.H., K.K., S. Kempa, R.D., S.K.F., D.N.M., N.W.)."},{"name":"Berlin Institute of Health, Germany (H.B., A.B., L.M., E.G.A., N.H., K.K., R.D., S.K.F., D.N.M., N.W.)."},{"name":"European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany (S.K.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik N.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation of Charit\u00e9-Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., N.H., K.K., J.F., M.G., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Germany (H.B., A.B., L.M., D.T., S.W., E.G.A., J.B., R.D., S.K.F., D.N.M., N.W.)."},{"name":"Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.B., A.B., L.M., A. 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