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We hypothesized that cardiac remodeling in swine\n RVH<\/jats:styled-content>\n is partly attributable to cardiac mitochondrial injury.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n After 12\u00a0weeks of hypercholesterolemic (\n HC<\/jats:styled-content>\n )\u2010\n RVH<\/jats:styled-content>\n or control (n=14 each), pigs were treated for another 4\u00a0weeks with vehicle or with the mitochondrial\u2010targeted peptide (\n MTP<\/jats:styled-content>\n ), Bendavia (0.1\u00a0mg\/kg subcutaneously, 5\u00a0days\/week), which stabilizes mitochondrial inner\u2010membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector\u2010computed tomography and oxygenation by blood\u2010oxygen\u2010level\u2013dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic\u2010reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex\u00a0vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert\u2010butyl hydroperoxide (\n tBHP<\/jats:styled-content>\n ) untreated or treated with\n MTP<\/jats:styled-content>\n . Chronic mitoprotection in\u00a0vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin\u2010sensitive sarcoplasmic reticulum Ca\n 2+<\/jats:sup>\n \u2010\n ATP<\/jats:styled-content>\n ase activity that declined in\n HC<\/jats:styled-content>\n \u2010\n RVH<\/jats:styled-content>\n normalized in\n MTP<\/jats:styled-content>\n \u2010treated pigs. Mitoprotection also improved\n LV<\/jats:styled-content>\n relaxation (E\/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in\n MTP<\/jats:styled-content>\n \u2010treated pigs. In\n tBHP<\/jats:styled-content>\n \u2010treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Chronic mitoprotection blunted myocardial hypertrophy, improved\n LV<\/jats:styled-content>\n relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained\n HC<\/jats:styled-content>\n \u2010\n RVH<\/jats:styled-content>\n , suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.003118","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T03:09:23Z","timestamp":1464750563000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension"],"prefix":"10.1161","volume":"5","author":[{"given":"Alfonso","family":"Eirin","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Ebrahimi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Hyo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Fiala","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Woollard","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"He","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Center, Sanford\u2010Burnham Medical Research Institute, Orlando, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramech C.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani N.","family":"Sabbah","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.S.","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Textor","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Lerman","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach O.","family":"Lerman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"},{"name":"Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-6686.2010.00161.x"},{"key":"e_1_3_3_3_2","first-page":"856","article-title":"The heart in atherosclerotic renovascular disease","volume":"4","author":"Green D","year":"2012","unstructured":"Green D, Kalra PA. 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