Editing Circadian rhythm (section)

==== Relationship with cardiovascular disease ====

One of the first studies to determine how disruption of circadian rhythms causes cardiovascular disease was performed in the Tau hamsters, which have a genetic defect in their circadian clock mechanism.<ref name="Circadian rhythm disorganization pr">{{cite journal | vauthors = Martino TA, Oudit GY, Herzenberg AM, Tata N, Koletar MM, Kabir GM, Belsham DD, Backx PH, Ralph MR, Sole MJ | title = Circadian rhythm disorganization produces profound cardiovascular and renal disease in hamsters | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 294 | issue = 5 | pages = R1675–R1683 | date = May 2008 | pmid = 18272659 | doi = 10.1152/ajpregu.00829.2007 | s2cid = 13356393 }}</ref> When maintained in a 24-hour light-dark cycle that was "out of sync" with their normal 22 circadian mechanism they developed profound cardiovascular and renal disease; however, when the Tau animals were raised for their entire lifespan on a 22-hour daily light-dark cycle they had a healthy cardiovascular system.<ref name="Circadian rhythm disorganization pr"/> The adverse effects of circadian misalignment on human physiology has been studied in the laboratory using a misalignment protocol,<ref>{{cite journal | vauthors = Scheer FA, Hilton MF, Mantzoros CS, Shea SA | title = Adverse metabolic and cardiovascular consequences of circadian misalignment | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 11 | pages = 4453–4458 | date = March 2009 | pmid = 19255424 | pmc = 2657421 | doi = 10.1073/pnas.0808180106 | doi-access = free | bibcode = 2009PNAS..106.4453S }}</ref><ref>{{cite journal | vauthors = Scheer FA, Michelson AD, Frelinger AL, Evoniuk H, Kelly EE, McCarthy M, Doamekpor LA, Barnard MR, Shea SA | title = The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors | journal = PLOS ONE | volume = 6 | issue = 9 | pages = e24549 | date = 2011 | pmid = 21931750 | pmc = 3169622 | doi = 10.1371/journal.pone.0024549 | doi-access = free | bibcode = 2011PLoSO...624549S }}</ref> and by studying shift workers.<ref name="pubmed.ncbi.nlm.nih.gov"/><ref>{{cite journal | vauthors = Rabinovich-Nikitin I, Lieberman B, Martino TA, Kirshenbaum LA | title = Circadian-Regulated Cell Death in Cardiovascular Diseases | journal = Circulation | volume = 139 | issue = 7 | pages = 965–980 | date = February 2019 | pmid = 30742538 | doi = 10.1161/CIRCULATIONAHA.118.036550 | s2cid = 73436800 | doi-access = free }}</ref><ref name="Kervezee 396–412"/> Circadian misalignment is associated with many risk factors of cardiovascular disease. High levels of the atherosclerosis biomarker, resistin, have been reported in shift workers indicating the link between circadian misalignment and plaque build up in arteries.<ref name="Kervezee 396–412">{{cite journal | vauthors = Kervezee L, Kosmadopoulos A, Boivin DB | title = Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances | journal = The European Journal of Neuroscience | volume = 51 | issue = 1 | pages = 396–412 | date = January 2020 | pmid = 30357975 | doi = 10.1111/ejn.14216 | s2cid = 53031343 | url = https://escholarship.mcgill.ca/concern/articles/gt54kt25z }}</ref> Additionally, elevated triacylglyceride levels (molecules used to store excess fatty acids) were observed and contribute to the hardening of arteries, which is associated with cardiovascular diseases including heart attack, stroke and heart disease.<ref name="Kervezee 396–412"/><ref name="Proper e147–e157">{{cite journal | vauthors = Proper KI, van de Langenberg D, Rodenburg W, Vermeulen RC, van der Beek AJ, van Steeg H, van Kerkhof LW | title = The Relationship Between Shift Work and Metabolic Risk Factors: A Systematic Review of Longitudinal Studies | language = English | journal = American Journal of Preventive Medicine | volume = 50 | issue = 5 | pages = e147–e157 | date = May 2016 | pmid = 26810355 | doi = 10.1016/j.amepre.2015.11.013 | hdl = 1874/346787 | hdl-access = free }}</ref> Shift work and the resulting circadian misalignment is also associated with hypertension.<ref name="pmid22211891" />