{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:00:09Z","timestamp":1790928009080,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Given an epidemiological association between hypertension and osteoarthritis, we aim to elucidate how vascular pathology triggers avascular articular cartilage loss by comparing vascular and joint phenotypes between spontaneously hypertensive rats and normotensive Wistar Kyoto rats at tissue, cellular, and molecular levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Systemic and local endothelial function were assessed via blood pressure monitoring and photoacoustic imaging of knee joints, respectively (n=5\u20136). Tissue and cellular damages in articular cartilage, subchondral bone, and synovium were systemically evaluated by radiological and histological examination (n=6). Endothelial transcriptional changes were delineated via bulk RNA\u2010seq (n=3). The secretome of human endothelial cells under oxidative stress was analyzed via proteomics to identify key factors in chondrocyte senescence (n=4). Captopril, an antihypertensive medication, was adopted as a tool to rescue chondrocyte senescence and osteoarthritis both in\u00a0vitro (n=3) and in\u00a0vivo (n=6).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Compared with Wistar Kyoto rats, spontaneously hypertensive rats exhibited higher blood pressure and local joint hypoxia with increased endothelial oxidative stress as early as 3 months old. Notably, these endothelial dysfunctions preceded the onset of structural joint damage. By 9\u2009months of age, spontaneously hypertensive rats developed osteoarthritis\u2010like pathology characterized by senescent chondrocyte accumulation and cartilage degradation, which could be mitigated by captopril. Transcriptomic and proteomic analyses of rat and human endothelial cells revealed upregulated IGFBPs (insulin\u2010like growth factor\u2010binding proteins). Among them, IGFBP6 was identified to induce chondrocyte senescence in\u00a0vitro. This effect can be modified by captopril treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Systemic vascular dysfunction may induce local joint damage with upregulation of endothelial IGFBPs secretion such as IGFBP6. This study highlights a potential therapeutic target for preventing joint structural damage by addressing endothelial dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.042132","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:46:36Z","timestamp":1765968396000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Endothelial Dysfunction Contributes to Chondrocyte Senescence Associated With Insulin\u2010Like Growth Factor\u2010Binding Protein\u20106 in a Spontaneously Hypertensive Rat Model"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-9364","authenticated-orcid":false,"given":"Yuqi","family":"Zhang","sequence":"first","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]},{"name":"Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5031-6500","authenticated-orcid":false,"given":"Karen","family":"Ching","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-1907","authenticated-orcid":false,"given":"Lanlan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2801-3626","authenticated-orcid":false,"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hong Kong Baptist University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu Ling","family":"Yip","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Lu","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-2424","authenticated-orcid":false,"given":"Zhongyu","family":"Liu","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Sun Yat\u2010sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZongWei","family":"Cai","sequence":"additional","affiliation":[{"name":"Hong Kong Baptist University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1786-6006","authenticated-orcid":false,"given":"Man Ting","family":"Au","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-7822","authenticated-orcid":false,"given":"Chunyi","family":"Wen","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University","place":["Kowloon Hong Kong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.40087"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3656-z"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.05.003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.11.007"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000515088"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050288"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4324"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar4494"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.12096"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1588907"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.099432"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193173"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.40928"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.08.006"},{"key":"e_1_3_2_16_2","unstructured":"Dhand NKK. 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