{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:33:27Z","timestamp":1791268407702,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Angiotensin II (AngII) infusion profoundly increases activity of calpains, calcium-dependent neutral cysteine proteases, in mice. Pharmacological inhibition of calpains attenuates AngII-induced aortic medial macrophage accumulation, atherosclerosis, and abdominal aortic aneurysm in mice. However, the precise functional contribution of leukocyte-derived calpains in AngII-induced vascular pathologies has not been determined. The purpose of this study was to determine whether calpains expressed in bone marrow (BM)\u2013derived cells contribute to AngII-induced atherosclerosis and aortic aneurysms in hypercholesterolemic mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              To study whether leukocyte calpains contributed to AngII-induced aortic pathologies, irradiated male low-density lipoprotein receptor\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice were repopulated with BM-derived cells that were either wild-type or overexpressed calpastatin, the endogenous inhibitor of calpains. Mice were fed a fat-enriched diet and infused with AngII (1000 ng\/kg per minute) for 4 weeks. Overexpression of calpastatin in BM-derived cells significantly attenuated AngII-induced atherosclerotic lesion formation in aortic arches, but had no effect on aneurysm formation. Using either BM-derived cells from calpain-1-deficient mice or mice with leukocyte-specific calpain-2 deficiency generated using cre-loxP recombination technology, further studies demonstrated that independent deficiency of either calpain-1 or -2 in leukocytes modestly attenuated AngII-induced atherosclerosis. Calpastatin overexpression significantly attenuated AngII-induced inflammatory responses in macrophages and spleen. Furthermore, calpain inhibition suppressed migration and adhesion of macrophages to endothelial cells in vitro. Calpain inhibition also significantly decreased hypercholesterolemia-induced atherosclerosis in the absence of AngII.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The present study demonstrates a pivotal role for BM-derived calpains in mediating AngII-induced atherosclerosis by influencing macrophage function.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.307285","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T05:04:37Z","timestamp":1457672677000},"page":"835-845","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Leukocyte Calpain Deficiency Reduces Angiotensin II\u2013Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice"],"prefix":"10.1161","volume":"36","author":[{"given":"Deborah A.","family":"Howatt","sequence":"first","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Balakrishnan","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J.","family":"Moorleghen","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latha","family":"Muniappan","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra L.","family":"Rateri","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhito A.","family":"Uchida","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Takano","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athar H.","family":"Chishti","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Baud","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkateswaran","family":"Subramanian","sequence":"additional","affiliation":[{"name":"From the Saha Cardiovascular Research Center (D.A.H., A.B., J.J.M., L.M., D.L.R.), and Department of Physiology (V.S.), University of Kentucky, Lexington; Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (H.A.U.); Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan (J.T., T.C.S.); Department of Developmental, Molecular, and Chemical Biology, Tufts University..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7818"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000085631.76095.64"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000254680.71485.92"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2002"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07222.x"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.217901"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034461"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8898-z"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)80015-U"},{"key":"e_1_3_5_12_2","first-page":"1679","article-title":"Differential sensitivity of FOS and JUN family members to calpains.","volume":"9","author":"Carillo S","year":"1994","unstructured":"Carillo S, Pariat M, Steff AM, Roux P, Etienne-Julan M, Lorca T, Piechaczyk M. 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