{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:41:31Z","timestamp":1790685691488,"version":"4.1.0"},"reference-count":180,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG061586, HL137647, HL151391"],"award-info":[{"award-number":["AG061586, HL137647, HL151391"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom11101482","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"1482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Biomolecules Orchestrating Cardiovascular Calcification"],"prefix":"10.3390","volume":"11","author":[{"given":"Yin","family":"Tintut","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Physiology, University of California-Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Orthopaedic Surgery, University of California-Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry M.","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda L.","family":"Demer","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Department of Physiology, University of California-Los Angeles, Los Angeles, CA 90095, USA"},{"name":"Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA"},{"name":"Department of Bioengineering, University of California-Los Angeles, Los Angeles, CA 90095, USA"},{"name":"The David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115392","DOI":"10.1016\/j.bone.2020.115392","article-title":"Pharmacological TNAP inhibition efficiently inhibits arterial media calcification in a warfarin rat model but deserves careful consideration of potential physiological bone formation\/mineralization impairment","volume":"137","author":"Opdebeeck","year":"2020","journal-title":"Bone"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23285","DOI":"10.1038\/srep23285","article-title":"Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques","volume":"6","author":"Curtze","year":"2016","journal-title":"Sci. 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