{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:56:53Z","timestamp":1791892613221,"version":"4.3.4"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Cardiovascular diseases (CVD) represent one of the major sequelae of obesity. On the other hand, the relationship between bone diseases and obesity remains unclear. An increasing number of biological and epidemiological studies suggest the presence of a link between atherosclerosis and osteoporosis, however, the precise molecular pathways underlying this close association remain poorly understood. The present work thus aimed to study Matrix Metalloproteinase 9 (MMP-9), as a proposed link between atherosclerosis and osteoporosis in high fat diet fed rats.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods and findings<\/jats:title><jats:p>40 rats were randomly divided into 4 groups: control, untreated atherosclerosis group, atherosclerotic rats treated with carvedilol (10mg\/kg\/d) and atherosclerotic rats treated with alendronate sodium (10mg\/kg\/d). After 8 weeks, blood samples were collected for estimation of Lipid profile (Total cholesterol, HDL, TGs), inflammatory markers (IL-6, TNF-\u03b1, CRP and NO) and Bone turnover markers (BTMs) (Alkaline phosphatase, osteocalcin and pyridinoline). Rats were then euthanized and the aortas and tibias were dissected for histological examination and estimation of MMP-9, N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX) and NF-kB expression. Induction of atherosclerosis via high fat diet and chronic stress induced a significant increase in BTMs, inflammatory markers and resulted in a state of dyslipidaemia. MMP-9 has also shown to be significantly increased in the untreated atherosclerosis rats and showed a significant correlation with all measured parameters. Interestingly, Carvedilol and bisphosphonate had almost equal effects restoring the measured parameters back to normal, partially or completely.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Conclusion<\/jats:title><jats:p>MMP-9 is a pivotal molecule that impact the atherogenic environment of the vessel wall. A strong cross talk exists between MMP-9, cytokine production and macrophage function. It also plays an important regulatory role in osteoclastogenesis. So, it may be a key molecule in charge for coupling CVD and bone diseases in high fat diet fed rats. Therefore, we suggest MMP-9 as a worthy molecule to be targeted pharmacologically in order to control both conditions simultaneously. Further studies are needed to support, to invest and to translate this hypothesis into clinical studies and guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0244650","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T18:00:50Z","timestamp":1613152850000},"page":"e0244650","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats"],"prefix":"10.1371","volume":"16","author":[{"given":"Maha","family":"Sabry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham","family":"Mostafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Rashed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Abdelgwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-584X","authenticated-orcid":true,"given":"Samaa","family":"Kamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2369-4052","authenticated-orcid":true,"given":"Suzanne","family":"Estaphan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"pone.0244650.ref001","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2147\/VHRM.S168946","article-title":"Obesity paradox in cardiovascular disease: where do we stand?","volume":"15","author":"S Carbone","year":"2019","journal-title":"Vasc Health Risk Manag"},{"issue":"2","key":"pone.0244650.ref002","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1590\/S0004-27302010000200010","article-title":"Obesity, diabetes mellitus and last but not least, osteoporosis","volume":"54","author":"FJ de Paula","year":"2010","journal-title":"Arquivos Brasileiros de Endocrinologia & Metabologia"},{"issue":"12","key":"pone.0244650.ref003","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.jnutbio.2009.10.002","article-title":"High fat diet-induced animal model of age-associated obesity and osteoporosis","volume":"21","author":"GV Halade","year":"2010","journal-title":"The Journal of nutritional biochemistry"},{"issue":"1","key":"pone.0244650.ref004","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1749-799X-6-30","article-title":"Effects of obesity on bone metabolism","volume":"6","author":"JJ Cao","year":"2011","journal-title":"Journal of orthopaedic surgery and research"},{"issue":"4","key":"pone.0244650.ref005","doi-asserted-by":"crossref","first-page":"e0122646","DOI":"10.1371\/journal.pone.0122646","article-title":"Bisphosphonates and risk of cardiovascular events: a meta-analysis","volume":"10","author":"DH Kim","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0244650.ref006","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1161\/CIRCRESAHA.110.216846","article-title":"Estrogen inhibits vascular calcification via vascular RANKL system: common mechanism of osteoporosis and vascular calcification","volume":"107","author":"MK Osako","year":"2010","journal-title":"Circulation research"},{"issue":"3","key":"pone.0244650.ref007","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jsha.2011.03.001","article-title":"Bone mineral density and coronary atherosclerosis","volume":"23","author":"S Hajsadeghi","year":"2011","journal-title":"Journal of the Saudi Heart Association"},{"issue":"1","key":"pone.0244650.ref008","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00223-015-0008-3","article-title":"Positive association between adipose tissue and bone stiffness","volume":"97","author":"R Berg","year":"2015","journal-title":"Calcified tissue international"},{"issue":"1","key":"pone.0244650.ref009","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/1354750X.2013.866165","article-title":"Serum levels and polymorphisms of matrix metalloproteinases (MMPs) in carotid artery atherosclerosis: higher MMP-9 levels are associated with plaque vulnerability","volume":"19","author":"D Silvello","year":"2014","journal-title":"Biomarkers"},{"issue":"2","key":"pone.0244650.ref010","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1101\/gad.268714.115","article-title":"MMP-9 facilitates selective proteolysis of the histone H3 tail at genes necessary for proficient osteoclastogenesis","volume":"30","author":"K Kim","year":"2016","journal-title":"Genes & development"},{"issue":"16","key":"pone.0244650.ref011","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.2174\/1381612824666180604112925","article-title":"MMPs are involved in osteoporosis and are correlated with cardiovascular diseases","volume":"24","author":"A Azevedo","year":"2018","journal-title":"Current pharmaceutical design"},{"issue":"3","key":"pone.0244650.ref012","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cell.2008.01.017","article-title":"Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone","volume":"132","author":"J Yang","year":"2008","journal-title":"Cell"},{"issue":"8","key":"pone.0244650.ref013","article-title":"The effect of soluble RAGE on inhibition of angiotensin II-mediated atherosclerosis in apolipoprotein E deficient mice","volume":"8","author":"D Lee","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"pone.0244650.ref014","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.neuroscience.2009.01.059","article-title":"Chronic social instability stress in female rats: a potential animal model for female depression","volume":"159","author":"C Herzog","year":"2009","journal-title":"Neuroscience"},{"issue":"3","key":"pone.0244650.ref015","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/15748855113086660010","article-title":"The potential effect of carvedilol against osteoporosis in ovariectomized rats","volume":"8","author":"V Boshra","year":"2013","journal-title":"Current Drug Therapy"},{"issue":"5","key":"pone.0244650.ref016","first-page":"571","article-title":"Effect of concurrent administration of alendronate sodium and retinol on development of changes in histomorphometric parameters of bones induced by ovariectomy in rats","volume":"56","author":"M Pytlik","year":"2004","journal-title":"Polish journal of pharmacology"},{"key":"pone.0244650.ref017","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/clinchem\/20.4.470","article-title":"Enzymatic determination of total serum cholesterol","volume":"20","author":"C Allian","year":"1974","journal-title":"Clin Chem"},{"key":"pone.0244650.ref018","first-page":"476","article-title":"Estimation of lipids by enzymatic method","volume":"19","author":"G Buccolo","year":"1973","journal-title":"Clin Chim Acta"},{"issue":"5","key":"pone.0244650.ref019","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0022-2275(20)42231-X","article-title":"Determination of high density lipoprotein-cholesterol in stored human plasma","volume":"21","author":"PS Bachorik","year":"1980","journal-title":"Journal of lipid research"},{"issue":"4","key":"pone.0244650.ref020","first-page":"645","article-title":"Serum TNF alpha levels: a prognostic marker for assessment of severity of malaria","volume":"30","author":"P Kinra","year":"2013","journal-title":"Trop Biomed"},{"issue":"12","key":"pone.0244650.ref021","doi-asserted-by":"crossref","first-page":"5802","DOI":"10.4049\/jimmunol.153.12.5802","article-title":"Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses","volume":"153","author":"JG Giri","year":"1994","journal-title":"The Journal of Immunology"},{"issue":"558","key":"pone.0244650.ref022","article-title":"Adenosine Receptor Stimulation Improves Glucocorticoid-Induced Osteoporosis in a Rat Model","volume":"8","author":"G Pizzino","year":"2017","journal-title":"Frontiers in Pharmacology"},{"issue":"4","key":"pone.0244650.ref023","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.bbrc.2010.06.008","article-title":"An ELISA-based method to quantify osteocalcin carboxylation in mice","volume":"397","author":"M Ferron","year":"2010","journal-title":"Biochemical and biophysical research communications"},{"issue":"4","key":"pone.0244650.ref024","doi-asserted-by":"crossref","first-page":"611","DOI":"10.4314\/tjpr.v17i4.7","article-title":"Bone turnover and oxidative stress markers in estrogendeficient rats treated with Marantodes pumilum leaves and roots: A comparative study","volume":"17","author":"TR Giaze","year":"2018","journal-title":"Tropical Journal of Pharmaceutical Research"},{"key":"pone.0244650.ref025","first-page":"2013","article-title":"Relevance of plasma obestatin and early arteriosclerosis in patients with type 2 diabetes mellitus","author":"P-y Gu","year":"2013","journal-title":"Journal of diabetes research"},{"issue":"3","key":"pone.0244650.ref026","first-page":"1807","article-title":"Dynamic expression of matrix metalloproteinases 2, 9 and 13 in ovariectomy-induced osteoporosis rats","volume":"16","author":"X Zheng","year":"2018","journal-title":"Experimental and therapeutic medicine"},{"issue":"1","key":"pone.0244650.ref027","doi-asserted-by":"crossref","first-page":"58","DOI":"10.5603\/FHC.a2016.0007","article-title":"Histological and Histochemical Methods: Theory and Practice. Scion Publishing, 2015, 571 pp","volume":"54","author":"Z Kmiec","year":"2016","journal-title":"Folia histochemica et cytobiologica"},{"key":"pone.0244650.ref028","volume-title":"Bancroft\u2019s theory and practice of histological techniques E-Book","author":"KS Suvarna","year":"2018"},{"issue":"2","key":"pone.0244650.ref029","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5114\/aoms.2011.22066","article-title":"Association between atherosclerosis and osteoporosis, the role of vitamin D","volume":"7","author":"OI Stojanovic","year":"2011","journal-title":"Archives of medical science: AMS"},{"issue":"9","key":"pone.0244650.ref030","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1161\/ATVBAHA.111.230904","article-title":"Bone Gla protein increases HIF-1\u03b1\u2013dependent glucose metabolism and induces cartilage and vascular calcification","volume":"31","author":"A Idelevich","year":"2011","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"issue":"1","key":"pone.0244650.ref031","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0021-9150(94)05395-Y","article-title":"Quantitation of the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta with dystrophic calcification","volume":"112","author":"H Hoshino","year":"1995","journal-title":"Atherosclerosis"},{"issue":"8","key":"pone.0244650.ref032","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1359\/jbmr.2000.15.8.1526","article-title":"Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study","volume":"15","author":"P Garnero","year":"2000","journal-title":"Journal of Bone and Mineral Research"},{"issue":"3","key":"pone.0244650.ref033","first-page":"719","article-title":"Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study","volume":"82","author":"P Vergnaud","year":"1997","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"6","key":"pone.0244650.ref034","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4103\/2230-8210.192914","article-title":"Bone turnover markers: Emerging tool in the management of osteoporosis","volume":"20","author":"S Shetty","year":"2016","journal-title":"Indian J Endocrinol Metab"},{"issue":"20","key":"pone.0244650.ref035","doi-asserted-by":"crossref","first-page":"11201","DOI":"10.1073\/pnas.1932554100","article-title":"Calcification in atherosclerosis: bone biology and chronic inflammation at the arterial crossroads","volume":"100","author":"TM Doherty","year":"2003","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"5","key":"pone.0244650.ref036","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00198-003-1550-9","article-title":"Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels","volume":"15","author":"P Pennisi","year":"2004","journal-title":"Osteoporosis international"},{"issue":"10","key":"pone.0244650.ref037","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1161\/01.RES.0000249379.55535.21","article-title":"Vascular calcification: pathobiological mechanisms and clinical implications","volume":"99","author":"RC Johnson","year":"2006","journal-title":"Circulation research"},{"issue":"3","key":"pone.0244650.ref038","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.bbadis.2016.12.003","article-title":"TNAP stimulates vascular smooth muscle cell trans-differentiation into chondrocytes through calcium deposition and BMP-2 activation: Possible implication in atherosclerotic plaque stability","volume":"1863","author":"M Fakhry","year":"2017","journal-title":"Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease"},{"issue":"1","key":"pone.0244650.ref039","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cmet.2012.11.012","article-title":"Vascular complications of diabetes: mechanisms of injury and protective factors","volume":"17","author":"C Rask-Madsen","year":"2013","journal-title":"Cell metabolism"},{"issue":"6","key":"pone.0244650.ref040","first-page":"391","article-title":"A critical review of the use of carvedilol in ischemic heart disease","volume":"12","author":"C Chen-Scarabelli","year":"2012","journal-title":"American Journal of Cardiovascular Drugs"},{"issue":"1","key":"pone.0244650.ref041","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1586\/erc.11.166","article-title":"Carvedilol: a third-generation \u03b2-blocker should be a first-choice \u03b2-blocker","volume":"10","author":"JJ DiNicolantonio","year":"2012","journal-title":"Expert review of cardiovascular therapy"},{"issue":"1","key":"pone.0244650.ref042","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s00223-013-9752-4","article-title":"Control of bone remodeling by the peripheral sympathetic nervous system","volume":"94","author":"F Elefteriou","year":"2014","journal-title":"Calcified tissue international"},{"issue":"2","key":"pone.0244650.ref043","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1080\/13547500902765140","article-title":"Potential implications of matrix metalloproteinase-9 in assessment and treatment of coronary artery disease","volume":"14","author":"Y Konstantino","year":"2009","journal-title":"Biomarkers"},{"issue":"5","key":"pone.0244650.ref044","doi-asserted-by":"crossref","DOI":"10.1016\/j.ahj.2006.02.029","article-title":"Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction","volume":"151","author":"E Cavusoglu","year":"2006","journal-title":"American heart journal"},{"issue":"6","key":"pone.0244650.ref045","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1189\/jlb.71.6.1012","article-title":"Oxidized low\u2010density and high\u2010density lipoproteins regulate the production of matrix metalloproteinase\u20101 and\u20109 by activated monocytes","volume":"71","author":"JA Ardans","year":"2002","journal-title":"Journal of leukocyte biology"},{"issue":"4","key":"pone.0244650.ref046","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3390\/biom9040129","article-title":"Matrix Metalloproteinase 9 as a Predictor of Coronary Atherosclerotic Plaque Instability in Stable Coronary Heart Disease Patients with Elevated Lipoprotein (a) Levels","volume":"9","author":"M Ezhov","year":"2019","journal-title":"Biomolecules"},{"issue":"06","key":"pone.0244650.ref047","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1160\/TH08-07-0469","article-title":"Vulnerable atherosclerotic plaque metalloproteinases and foam cell phenotypes","volume":"101","author":"AC Newby","year":"2009","journal-title":"Thrombosis and haemostasis"},{"issue":"2","key":"pone.0244650.ref048","first-page":"247","article-title":"MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr-\/-Apob100\/100 mouse","volume":"28","author":"D W\u00e5gs\u00e4ter","year":"2011","journal-title":"International journal of molecular medicine"},{"key":"pone.0244650.ref049","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pharmthera.2018.08.012","article-title":"Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis. Pharmacology &","volume":"193","author":"M Lacy","year":"2019","journal-title":"Therapeutics"},{"issue":"12","key":"pone.0244650.ref050","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1136\/heartjnl-2013-305130","article-title":"The genetic basis for aortic aneurysmal disease","volume":"100","author":"A Saratzis","year":"2014","journal-title":"Heart"},{"issue":"2","key":"pone.0244650.ref051","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/j.1365-2249.2009.03949.x","article-title":"Inhibition of matrix metalloproteinase\u20109 activity improves coronary outcome in an animal model of Kawasaki disease","volume":"157","author":"A Lau","year":"2009","journal-title":"Clinical & Experimental Immunology"},{"issue":"12","key":"pone.0244650.ref052","first-page":"2831","article-title":"Involvement of protein kinase C in TNF\u03b1 regulation of trabecular matrix metalloproteinases and TIMPs","volume":"42","author":"JP Alexander","year":"2001","journal-title":"Investigative ophthalmology & visual science"},{"issue":"3","key":"pone.0244650.ref053","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.trsl.2006.09.001","article-title":"Matrix metalloproteinases in premature coronary atherosclerosis: influence of inhibitors, inflammation, and genetic polymorphisms","volume":"149","author":"S Nanni","year":"2007","journal-title":"Translational Research"},{"issue":"1","key":"pone.0244650.ref054","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1471-2407-12-26","article-title":"TGF-\u03b21 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1\/2 in highly invasive breast cancer cells","volume":"12","author":"LR Gomes","year":"2012","journal-title":"BMC cancer"},{"issue":"5","key":"pone.0244650.ref055","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1161\/ATVBAHA.107.139592","article-title":"A pathway-dependent on apoE, ApoAI, and ABCA1 determines formation of buoyant high-density lipoprotein by macrophage foam cells","volume":"27","author":"PG Yancey","year":"2007","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"issue":"08","key":"pone.0244650.ref056","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1160\/TH06-10-0561","article-title":"Evaluation of antibodies to oxidized low-density lipoprotein and assessment of C-reactive protein in acute coronary syndrome and stable coronary artery disease","volume":"98","author":"P Soltesz","year":"2007","journal-title":"Thrombosis and haemostasis"},{"issue":"5","key":"pone.0244650.ref057","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1194\/jlr.M700535-JLR200","article-title":"Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats","volume":"49","author":"U Singh","year":"2008","journal-title":"Journal of lipid research"},{"issue":"5","key":"pone.0244650.ref058","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.ajpath.2013.01.022","article-title":"Peptide inhibitor of NF-\u03baB translocation ameliorates experimental atherosclerosis","volume":"182","author":"B Mallavia","year":"2013","journal-title":"The American journal of pathology"},{"issue":"9","key":"pone.0244650.ref059","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1111\/j.1582-4934.2010.01082.x","article-title":"Increased expression of bFGF is associated with carotid atherosclerotic plaques instability engaging the NF-\u03baB pathway","volume":"14","author":"F Sigala","year":"2010","journal-title":"J Cell Mol Med"},{"issue":"1","key":"pone.0244650.ref060","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12872-016-0362-8","article-title":"Wnt signaling contributes to vascular calcification by induction of matrix metalloproteinases","volume":"16","author":"C Freise","year":"2016","journal-title":"BMC cardiovascular disorders"},{"key":"pone.0244650.ref061","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12944-016-0191-x","article-title":"Markers of increased atherosclerotic risk in patients with chronic kidney disease: a preliminary study","volume":"15","author":"A Gluba-Brz\u00f3zka","year":"2016","journal-title":"Lipids in health and disease"},{"issue":"7","key":"pone.0244650.ref062","first-page":"888","article-title":"CLINICAL PERSPECTIVE","volume":"115","author":"Rn Martos","year":"2007","journal-title":"Circulation"},{"issue":"4","key":"pone.0244650.ref063","first-page":"598","article-title":"Matrix metalloproteinase-9 regulates graft bone resorption","volume":"76","author":"M Lu","year":"2006","journal-title":"The Angle orthodontist"},{"issue":"5","key":"pone.0244650.ref064","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1124\/mol.105.020776","article-title":"Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis","volume":"69","author":"K Thompson","year":"2006","journal-title":"Molecular pharmacology"},{"issue":"23","key":"pone.0244650.ref065","doi-asserted-by":"crossref","first-page":"11438","DOI":"10.1158\/0008-5472.CAN-07-1882","article-title":"Amino-biphosphonate\u2013mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma","volume":"67","author":"C Melani","year":"2007","journal-title":"Cancer research"},{"issue":"6","key":"pone.0244650.ref066","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1161\/01.RES.0000241428.82502.d4","article-title":"Adenosine inhibits matrix metalloproteinase-9 secretion by neutrophils: implication of A2a receptor and cAMP\/PKA\/Ca2+ pathway","volume":"99","author":"I Ernens","year":"2006","journal-title":"Circulation research"},{"issue":"11","key":"pone.0244650.ref067","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.freeradbiomed.2007.08.010","article-title":"Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and-9 in experimental atherosclerosis","volume":"43","author":"T-C Wu","year":"2007","journal-title":"Free Radical Biology and Medicine"},{"issue":"7","key":"pone.0244650.ref068","doi-asserted-by":"crossref","first-page":"e66391","DOI":"10.1371\/journal.pone.0066391","article-title":"Carvedilol decrease IL-1\u03b2 and TNF-\u03b1, inhibits MMP-2, MMP-9, COX-2, and RANKL expression, and up-regulates OPG in a rat model of periodontitis","volume":"8","author":"RF de Araujo Junior","year":"2013","journal-title":"PLoS One"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T03:34:14Z","timestamp":1697859254000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244650"}},"subtitle":[],"editor":[{"given":"Dominique","family":"Heymann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,11]]},"references-count":68,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0244650","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,11]]}}}