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Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac\u2010targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new \u201cwhole\u2010systems\u201d approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system\u2010wide endothelial dysfunction in HFpEF.<\/jats:p>","DOI":"10.1155\/2017\/4865756","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T21:04:14Z","timestamp":1497906254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-4133","authenticated-orcid":false,"given":"Andreas B.","family":"Gevaert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Lemmens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan J.","family":"Vrints","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7686-2668","authenticated-orcid":false,"given":"Emeline M.","family":"Van Craenenbroeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,19]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300268"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14285-7"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1313731"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr161"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv132"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.735"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051530"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.83"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.092"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1989.69.4.1228"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00994-X"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jet256"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000153349.77489.CF"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00049.2015"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.11909\/j.issn.1671-5411.2015.03.013"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)00189-7"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.23.3095"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.24.2709"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.01.009"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.454"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.939959"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2006"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2002"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH05-01-0038"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/174782"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.22"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2009.12.009"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.10.047"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi001"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.6.2254"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.07.236"},{"key":"e_1_2_12_33_2","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.rec.2011.10.004","article-title":"Noninvasive assessment of endothelial function in clinical practice","volume":"65","author":"Arrebola-Moreno A. 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