PMID- 32451732 OWN - NLM STAT- MEDLINE DCOM- 20210709 LR - 20210709 IS - 1435-1803 (Electronic) IS - 0300-8428 (Print) IS - 0300-8428 (Linking) VI - 115 IP - 4 DP - 2020 May 25 TI - Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities. PG - 39 LID - 10.1007/s00395-020-0798-y [doi] LID - 39 AB - Heart failure with preserved ejection fraction (HFpEF) is a complex heterogeneous disease for which our pathophysiological understanding is still limited and specific prevention and treatment strategies are lacking. HFpEF is characterised by diastolic dysfunction and cardiac remodelling (fibrosis, inflammation, and hypertrophy). Recently, microvascular dysfunction and chronic low-grade inflammation have been proposed to participate in HFpEF development. Furthermore, several recent studies demonstrated the occurrence of generalized lymphatic dysfunction in experimental models of risk factors for HFpEF, including obesity, hypercholesterolaemia, type 2 diabetes mellitus (T2DM), hypertension, and aging. Here, we review the evidence for a combined role of coronary (micro)vascular dysfunction and lymphatic vessel alterations in mediating key pathological steps in HFpEF, including reduced cardiac perfusion, chronic low-grade inflammation, and myocardial oedema, and their impact on cardiac metabolic alterations (oxygen and nutrient supply/demand imbalance), fibrosis, and cardiomyocyte stiffness. We focus primarily on HFpEF caused by metabolic risk factors, such as obesity, T2DM, hypertension, and aging. FAU - Cuijpers, Ilona AU - Cuijpers I AD - Center for Molecular and Vascular Biology, KU Leuven, Herestraat 49, bus 911, 3000, Leuven, Belgium. AD - Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. FAU - Simmonds, Steven J AU - Simmonds SJ AD - Center for Molecular and Vascular Biology, KU Leuven, Herestraat 49, bus 911, 3000, Leuven, Belgium. FAU - van Bilsen, Marc AU - van Bilsen M AD - Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. FAU - Czarnowska, Elzbieta AU - Czarnowska E AD - Department of Pathology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730, Warsaw, Poland. FAU - Gonzalez Miqueo, Arantxa AU - Gonzalez Miqueo A AD - Program of Cardiovascular Disease, Centro de Investigacion Medica Aplicada (CIMA), Universidad de Navarra, IdiSNA, Avda. Pio XII 55, 31008, Pamplona, Spain. AD - Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Av. Monforte de Lemos 3-5, 28029, Madrid, Spain. FAU - Heymans, Stephane AU - Heymans S AD - Center for Molecular and Vascular Biology, KU Leuven, Herestraat 49, bus 911, 3000, Leuven, Belgium. AD - Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. AD - Netherlands Heart Institute, Holland Heart House, Moreelsepark 1, 3511, Utrecht, The Netherlands. FAU - Kuhn, Annika R AU - Kuhn AR AD - Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. FAU - Mulder, Paul AU - Mulder P AD - Institut National de la Sante et de la Recherche Medicale (Inserm) UMR1096, Faculty of Medicine and Pharmacy, Normandy University, 22 Boulevard Gambetta, 76183, Rouen, France. FAU - Ratajska, Anna AU - Ratajska A AD - Department of Pathology, Medical University of Warsaw, Chalubinskiego 5, 02-004, Warsaw, Poland. FAU - Jones, Elizabeth A V AU - Jones EAV AD - Center for Molecular and Vascular Biology, KU Leuven, Herestraat 49, bus 911, 3000, Leuven, Belgium. liz.jones@kuleuven.be. AD - Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. liz.jones@kuleuven.be. FAU - Brakenhielm, Ebba AU - Brakenhielm E AD - Institut National de la Sante et de la Recherche Medicale (Inserm) UMR1096, Faculty of Medicine and Pharmacy, Normandy University, 22 Boulevard Gambetta, 76183, Rouen, France. ebba.brakenhielm@univ-rouen.fr. LA - eng GR - LYMIT-DIS 2016/European Research Area Network Cardiovascular disease/International GR - Macro ERA 2016/European Research Area Network Cardiovascular disease/International GR - GOH7716N/Fonds Wetenschappelijk Onderzoek/International GR - 1160718N/Fonds Wetenschappelijk Onderzoek/International GR - G091018N/Fonds Wetenschappelijk Onderzoek/International GR - 16-ECVD-0004/Agence Nationale de la Recherche/International GR - ZonMw 2016T091/Stichting voor de Technische Wetenschappen/International GR - Vidi 91796338/Stichting voor de Technische Wetenschappen/International GR - AC16/00020/Instituto de Salud Carlos III/International GR - CB16/11/00483/Instituto de Salud Carlos III/International GR - PI18/01469/Instituto de Salud Carlos III/International GR - ERA-CVD/LyMitDis/1/2017/Narodowe Centrum Badan i Rozwoju/International GR - CVON2016-Early HFPEF, 2015-10/Hartstichting/International GR - CVON She-PREDICTS, grant 2017-21/Hartstichting/International GR - CPER/FEDER 2015 (DO-IT)/ontrat de Plan Etat-Region - Fonds Europeen de Developpement Regional/International GR - CPER/FEDER 2016 (PACT-CBS)/ontrat de Plan Etat-Region - Fonds Europeen de Developpement Regional/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200525 PL - Germany TA - Basic Res Cardiol JT - Basic research in cardiology JID - 0360342 SB - IM MH - Aging/pathology MH - Animals MH - Diabetes Mellitus, Type 2/complications MH - Endothelium, Vascular/*pathology MH - Heart Failure/etiology/metabolism/*physiopathology MH - Humans MH - Hypertension/complications MH - Lymphatic Vessels/*pathology MH - Microvessels/pathology MH - Obesity/complications PMC - PMC7248044 OTO - NOTNLM OT - Cardiac lymphatic dysfunction OT - Cardiac metabolism OT - Coronary microvascular dysfunction OT - Heart failure with preserved ejection fraction OT - Inflammation OT - Myocardial fibrosis COIS- The authors declare that they have no conflict of interest. EDAT- 2020/05/27 06:00 MHDA- 2021/07/10 06:00 PMCR- 2020/05/25 CRDT- 2020/05/27 06:00 PHST- 2020/04/02 00:00 [received] PHST- 2020/05/13 00:00 [accepted] PHST- 2020/05/27 06:00 [entrez] PHST- 2020/05/27 06:00 [pubmed] PHST- 2021/07/10 06:00 [medline] PHST- 2020/05/25 00:00 [pmc-release] AID - 10.1007/s00395-020-0798-y [pii] AID - 798 [pii] AID - 10.1007/s00395-020-0798-y [doi] PST - epublish SO - Basic Res Cardiol. 2020 May 25;115(4):39. doi: 10.1007/s00395-020-0798-y.