{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:19:32Z","timestamp":1792001972601,"version":"4.4.0"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Vascular endothelial cells play an important role in regulating peripheral circulation by modulating arterial tone in the microvasculature. Elevated intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels are required in endothelial cells to induce smooth muscle relaxation via endothelium-dependent mechanisms such as nitric oxide production, prostacyclin, and endothelial cell hyperpolarization. It is well established that exogenous administration of acetylcholine can increase intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentrations, followed by endothelium-dependent vasodilation. Although endogenous acetylcholine's regulation of vascular tone remains debatable, recent studies have reported that endogenously derived acetylcholine, but not neuronal cell-derived acetylcholine, is a key modulator of endothelial cell function. In this minireview, we summarize the current knowledge of the non-neuronal cholinergic system (NNCS) in vascular function, particularly vascular endothelial cell function, which contributes to blood pressure regulation. We also discuss the possible pathophysiological impact of endothelial NNCS, which may induce the development of vascular diseases due to endothelial dysfunction, and the potential of endothelial NNCS as a novel therapeutic target for endothelial dysfunction in the early stages of metabolic syndrome, diabetes, and hypertension.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2024.1388528","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T01:16:24Z","timestamp":1715735784000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Non-neuronal cell-derived acetylcholine, a key modulator of the vascular endothelial function in health and disease"],"prefix":"10.3389","volume":"11","author":[{"given":"Takashi","family":"Sonobe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Kakinuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1161\/ATVBAHA.116.308339","article-title":"Microvascular endothelial dysfunction in sedentary, obese humans is mediated by NADPH oxidase: influence of exercise training","volume":"36","author":"La Favor","year":"2016","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1152\/japplphysiol.00837.2013","article-title":"Impact of reduced daily physical activity on conduit artery flow-mediated dilation and circulating endothelial microparticles","volume":"115","author":"Boyle","year":"2013","journal-title":"J Appl Physiol (1985)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1113\/EP085238","article-title":"Impact of prolonged sitting on lower and upper limb micro- and macrovascular dilator function","volume":"100","author":"Restaino","year":"2015","journal-title":"Exp Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1056\/NEJM199007053230105","article-title":"Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension","volume":"323","author":"Panza","year":"1990","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/BF00429099","article-title":"Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus","volume":"35","author":"McVeigh","year":"1992","journal-title":"Diabetologia"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1172\/JCI118709","article-title":"Obesity\/insulin resistance is associated with endothelial dysfunction. 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