{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:55:51Z","timestamp":1792000551995,"version":"4.4.0"},"reference-count":187,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p>Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) through the transsulfuration pathway. H<jats:sub>2<\/jats:sub>S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine \u03b2-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency have provided invaluable insights into the pathological effects of transsulfuration impairment and of both mild and severe HHcy. However, studies have also highlighted the complexity of HHcy and the need to explore the specific details of Hcy metabolism in addition to Hcy levels per se. There has been a relative paucity of work addressing the dysfunctional H<jats:sub>2<\/jats:sub>S production in CBS deficiency that may contribute to, or even create, HHcy-associated pathologies. Experiments using CBS knockout mice, both homozygous (\u2212\/\u2212) and heterozygous (+\/\u2212), have provided 15 years of new knowledge and are the focus of this review. These murine models present the opportunity to study a specific mechanism for HHcy that matches one of the etiologies in many human patients. Therefore, the goal of this review was to integrate and highlight the critical information gained thus far from models of CBS deficiency and draw attention to critical gaps in knowledge, with particular emphasis on the modulation of H<jats:sub>2<\/jats:sub>S metabolism. We include findings from human and animal studies to identify important opportunities for future investigation that should be aimed at generating new basic and clinical understanding of the role of CBS and transsulfuration in cardiovascular and neurovascular disease.<\/jats:p>","DOI":"10.1152\/ajpheart.00598.2010","type":"journal-article","created":{"date-parts":[[2010,10,23]],"date-time":"2010-10-23T01:11:18Z","timestamp":1287796278000},"page":"H13-H26","source":"Crossref","is-referenced-by-count":98,"title":["Vascular complications of cystathionine \u03b2-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research"],"prefix":"10.1152","volume":"300","author":[{"suffix":"Jr.","given":"Richard S.","family":"Beard","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Idaho State University, Pocatello, Idaho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn 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