{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:24:46Z","timestamp":1790897086310,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["67724, 91469, 102738, 112330, 138720, 144626, 150881"],"award-info":[{"award-number":["67724, 91469, 102738, 112330, 138720, 144626, 150881"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["23039"],"award-info":[{"award-number":["23039"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20 Merit 35120374"],"award-info":[{"award-number":["20 Merit 35120374"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["15CVD04"],"award-info":[{"award-number":["15CVD04"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Primary cilia are non-motile plasma membrane extrusions that display a variety of receptors and mechanosensors. Loss of function results in ciliopathies, which have been strongly linked with congenital heart disease, as well as abnormal development and function of most organ systems. Adults with congenital heart disease have high rates of acquired heart failure, and usually die from a cardiac cause. Here we explore primary cilia\u2019s role in acquired heart disease. Intraflagellar Transport 88 knockout results in reduced primary cilia, and knockout from cardiac endothelium produces myxomatous degeneration similar to mitral valve prolapse seen in adult humans. Induced primary cilia inactivation by other mechanisms also produces excess myocardial hypertrophy and altered scar architecture after ischemic injury, as well as hypertension due to a lack of vascular endothelial nitric oxide synthase activation and the resultant left ventricular dysfunction. Finally, primary cilia have cell-to-cell transmission capacity which, when blocked, leads to progressive left ventricular hypertrophy and heart failure, though this mechanism has not been fully established. Further research is still needed to understand primary cilia\u2019s role in adult cardiac pathology, especially heart failure.<\/jats:p>","DOI":"10.3390\/cells11060960","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T12:58:36Z","timestamp":1647003516000},"page":"960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Primary Cilia and Their Role in Acquired Heart Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Zachariah E.","family":"Hale","sequence":"first","affiliation":[{"name":"Department of Internal Medicine-Pediatrics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Sadoshima","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e007907","DOI":"10.1161\/JAHA.117.007907","article-title":"Adult congenital heart disease in a nationwide population 2000\u20132014: Epidemiological trends, arrhythmia, and standardized mortality ratio","volume":"7","author":"Wu","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e017704","DOI":"10.1161\/JAHA.120.017704","article-title":"Survival in children with congenital heart disease: Have we reached a peak at 97%?","volume":"9","author":"Mandalenakis","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCULATIONAHA.115.019307","article-title":"Congenital heart defects in the United States","volume":"134","author":"Gilboa","year":"2016","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0735-1097(00)00682-3","article-title":"Long-term outcome in congenitally corrected transposition of the great arteries: A multi-institutional study","volume":"36","author":"Graham","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1161\/CIRCRESAHA.116.308996","article-title":"Heart failure in pediatric patients with congenital heart disease","volume":"120","author":"Hinton","year":"2017","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.amjcard.2005.10.065","article-title":"Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery","volume":"97","author":"Norozi","year":"2006","journal-title":"Am. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1136\/heartjnl-2020-316791","article-title":"Predicting sudden cardiac death in adults with congenital heart disease","volume":"107","author":"Oliver","year":"2021","journal-title":"Heart"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1001\/jamacardio.2019.5459","article-title":"Diastolic heart failure in patients with the fontan circulation: A Review","volume":"5","author":"Budts","year":"2020","journal-title":"JAMA Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Inai, K. (2021). Biomarkers for heart failure and prognostic prediction in patients with Fontan circulation. Pediatr. Int.","DOI":"10.1111\/ped.14983"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF00297476","article-title":"Primary 9+0 cilia in the embryonic and the adult human heart","volume":"151","author":"Myklebust","year":"1977","journal-title":"Anat. Embryol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1242\/jcs.050377","article-title":"The primary cilium at a glance","volume":"123","author":"Satir","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4161\/org.28910","article-title":"The primary cilium: Guardian of organ development and homeostasis","volume":"10","author":"Fry","year":"2013","journal-title":"Organogenesis"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, X., Yang, S., Deepak, V., Chinipardaz, Z., and Yang, S. (2021). Identification of cilia in different mouse tissues. Cells, 10.","DOI":"10.3390\/cells10071623"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nature14269","article-title":"Global genetic analysis in mice unveils central role for cilia in congenital heart disease","volume":"521","author":"Li","year":"2015","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2020.04.017","article-title":"Role of cilia in the pathogenesis of congenital heart disease","volume":"110","author":"Gabriel","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.1073\/pnas.90.12.5519","article-title":"A motility in the eukaryotic flagellum unrelated to flagellar beating","volume":"90","author":"Kozminski","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ng.3558","article-title":"The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery","volume":"48","author":"Toriyama","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118216","DOI":"10.1016\/j.lfs.2020.118216","article-title":"Disruption of endothelial cell intraflagellar transport protein 88 exacerbates doxorubicin-induced cardiotoxicity","volume":"260","author":"Luu","year":"2020","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/2046-2530-1-23","article-title":"Multiple essential roles for primary cilia in heart development","volume":"1","author":"Willaredt","year":"2012","journal-title":"Cilia"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Moore, K., Moore, R., Wang, C., and Norris, R.A. (2020). Tugging at the heart strings: The septin cytoskeleton in heart development and disease. J. Cardiovasc. Dev. Dis., 7.","DOI":"10.3390\/jcdd7010003"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41581-019-0143-6","article-title":"Structure and function of polycystins: Insights into polycystic kidney disease","volume":"15","author":"Douguet","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/sj.leu.2403334","article-title":"FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23)","volume":"18","author":"Kojima","year":"2004","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3389\/fcell.2016.00122","article-title":"Septin mutations in human cancers","volume":"4","author":"Angelis","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fcell.2021.765085","article-title":"The structural biology of septins and their filaments: An update","volume":"9","author":"Cavini","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/S0002-9440(10)65743-4","article-title":"Identification of septins in neurofibrillary tangles in Alzheimer\u2019s disease","volume":"153","author":"Kinoshita","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.tcb.2021.06.001","article-title":"The ciliary impact of nonciliary gene mutations","volume":"31","author":"Lovera","year":"2021","journal-title":"Trends Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/ncb3201","article-title":"An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes","volume":"17","author":"Wheway","year":"2015","journal-title":"Nat. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2046-2530-2-7","article-title":"The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium","volume":"2","author":"Wheway","year":"2013","journal-title":"Cilia"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Van Dam, T.J.P., Kennedy, J., van der Lee, R., de Vrieze, E., Wunderlich, K.A., Rix, S., Dougherty, G.W., Lambacher, N.J., Li, C., and Jensen, V.L. (2019). CiliaCarta: An integrated and validated compendium of ciliary genes. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216705"},{"key":"ref_30","first-page":"318","article-title":"A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome","volume":"99","author":"Nicaise","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.tcb.2016.08.002","article-title":"The cilium: Cellular antenna and central processing unit","volume":"27","author":"Malicki","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.devcel.2017.12.003","article-title":"CRISPR screens uncover genes that regulate target cell sensitivity to the morphogen sonic hedgehog","volume":"44","author":"Pusapati","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41588-018-0054-7","article-title":"A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies","volume":"50","author":"Breslow","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Larsen, L.J., and M\u00f8ller, L.B. (2020). Crosstalk of hedgehog and mTORC1 pathways. Cells, 9.","DOI":"10.3390\/cells9102316"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"a028175","DOI":"10.1101\/cshperspect.a028175","article-title":"Primary cilia and mammalian hedgehog signaling","volume":"9","author":"Bangs","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Morleo, M., and Franco, B. (2019). The autophagy-cilia axis: An intricate relationship. Cells, 8.","DOI":"10.3390\/cells8080905"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nrg2774","article-title":"The primary cilium: A signalling centre during vertebrate development","volume":"11","author":"Goetz","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/s41419-019-2184-y","article-title":"Primary cilia mediate mitochondrial stress responses to promote dopamine neuron survival in a Parkinson\u2019s disease model","volume":"10","author":"Bae","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1038\/s41598-021-83418-3","article-title":"Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer","volume":"11","author":"Lee","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Atkinson, K.F., Sherpa, R.T., and Nauli, S.M. (2019). The Role of the primary cilium in sensing extracellular pH. Cells, 8.","DOI":"10.3390\/cells8070704"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Collins, I., and Wann, A. (2020). Regulation of the extracellular matrix by ciliary machinery. Cells, 9.","DOI":"10.3390\/cells9020278"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00467-010-1731-7","article-title":"Ciliopathies: An expanding disease spectrum","volume":"26","author":"Waters","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/ajmg.c.30231","article-title":"Making sense of cilia in disease: The human ciliopathies","volume":"151C","author":"Baker","year":"2009","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2174\/138920211795677912","article-title":"Alstrom syndrome: Genetics and clinical overview","volume":"12","author":"Marshall","year":"2011","journal-title":"Curr. Genom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4103\/0973-029X.110716","article-title":"Ellis-van Creveld syndrome: A rare clinical entity","volume":"17","author":"Kamal","year":"2013","journal-title":"J. Oral Maxillofac. Pathol. JOMFP"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/ajmg.a.33892","article-title":"Clinical insights gained from eight new cases and review of reported cases with Jeune syndrome (asphyxiating thoracic dystrophy)","volume":"155","author":"Adam","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.pediatrneurol.2020.01.012","article-title":"Clinical and molecular diagnosis of joubert syndrome and related disorders","volume":"106","author":"Devi","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-3-319-95046-4_26","article-title":"Leber congenital amaurosis","volume":"1085","author":"Tsang","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ejmg.2010.10.004","article-title":"Molecular diagnosis reveals genetic heterogeneity for the overlapping MKKS and BBS phenotypes","volume":"54","author":"Schaefer","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3389\/fped.2017.00244","article-title":"Meckel-Gruber syndrome: An update on diagnosis, clinical management, and research advances","volume":"5","author":"Hartill","year":"2017","journal-title":"Front. Pediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/nep.13393","article-title":"Nephronophthisis: A review of genotype\u2013phenotype correlation","volume":"23","author":"Luo","year":"2018","journal-title":"Nephrology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-3-319-95046-4_34","article-title":"Ciliopathy: Senior-L\u00f8ken syndrome","volume":"1085","author":"Tsang","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ajhg.2010.04.012","article-title":"Cranioectodermal dysplasia, sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene","volume":"86","author":"Eggenschwiler","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00404-004-0696-9","article-title":"Short rib-polydactyly syndrome","volume":"272","author":"Naki","year":"2004","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1161\/CIRCULATIONAHA.117.028752","article-title":"Fibroblast primary cilia are required for cardiac fibrosis","volume":"139","author":"Villalobos","year":"2019","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zhang, H., Chalothorn, D., and Faber, J.E. (2019). Collateral vessels have unique endothelial and smooth muscle cell phenotypes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153608"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1126\/scitranslmed.aax0290","article-title":"Primary cilia defects causing mitral valve prolapse","volume":"11","author":"Toomer","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13630-018-0058-z","article-title":"Evidence of primary cilia in the developing rat heart","volume":"7","author":"Kaur","year":"2018","journal-title":"Cilia"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Williams, K., Carson, J., and Lo, C. (2019). Genetics of congenital heart disease. Biomolecules, 9.","DOI":"10.3390\/biom9120879"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1161\/CIRCULATIONAHA.119.038376","article-title":"Defects in the Exocyst-Cilia machinery cause bicuspid aortic valve disease and aortic stenosis","volume":"140","author":"Fulmer","year":"2019","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1161\/CIRCULATIONAHA.113.006702","article-title":"Epidemiology and pathophysiology of mitral valve prolapse: New insights into disease progression, genetics, and molecular basis","volume":"129","author":"Delling","year":"2014","journal-title":"Circulation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature14670","article-title":"Mutations in DCHS1 cause mitral valve prolapse","volume":"525","author":"Durst","year":"2015","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/dvdy.24524","article-title":"A role for primary cilia in aortic valve development and disease","volume":"246","author":"Toomer","year":"2017","journal-title":"Dev. Dyn."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1161\/CIRCRESAHA.116.305381","article-title":"Getting to the heart of the matter: New insights into cardiac fibrosis","volume":"116","author":"Leask","year":"2015","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jacc.2018.07.006","article-title":"Mitral Valve Prolapse: A Disease of Valve and Ventricle","volume":"72","author":"Levine","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.jacc.2018.06.048","article-title":"Myocardial fibrosis in patients with primary mitral regurgitation with and without prolapse","volume":"72","author":"Kitkungvan","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s12265-012-9406-3","article-title":"The Extracellular matrix modulates fibroblast phenotype and function in the infarcted myocardium","volume":"5","author":"Dobaczewski","year":"2012","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nm1613","article-title":"Endothelial-to-mesenchymal transition contributes to cardiac fibrosis","volume":"13","author":"Zeisberg","year":"2007","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1038\/s41598-020-61292-9","article-title":"Endothelial-specific Loss of IFT88 promotes endothelial-to-mesenchymal transition and exacerbates bleomycin-induced pulmonary fibrosis","volume":"10","author":"Singh","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1161\/CIRCRESAHA.110.231860","article-title":"Lack of primary cilia primes shear-induced endothelial-to-mesenchymal transition","volume":"108","author":"Egorova","year":"2011","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.semcdb.2017.08.036","article-title":"Primary cilia: Cell and molecular mechanosensors directing whole tissue function","volume":"71","author":"Spasic","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.atherosclerosis.2018.06.818","article-title":"Role of endothelial primary cilia as fluid mechanosensors on vascular health","volume":"275","author":"Luu","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1161\/CIRCULATIONAHA.107.710111","article-title":"Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1","volume":"117","author":"Nauli","year":"2008","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pala, R., Jamal, M., Alshammari, Q., and Nauli, S.M. (2018). The roles of primary cilia in cardiovascular diseases. Cells, 7.","DOI":"10.3390\/cells7120233"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1161\/CIRCULATIONAHA.105.590018","article-title":"Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress","volume":"113","author":"Cheng","year":"2006","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.atherosclerosis.2007.05.030","article-title":"Endothelial primary cilia in areas of disturbed flow are at the base of atherosclerosis","volume":"196","author":"Hierck","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cm.21183","article-title":"Oscillatory fluid flow influences primary cilia and microtubule mechanics","volume":"71","author":"Espinha","year":"2014","journal-title":"Cytoskeleton"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"156","DOI":"10.15252\/embr.201541019","article-title":"Endothelial primary cilia inhibit atherosclerosis","volume":"17","author":"Dinsmore","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1053\/j.ajkd.2011.01.023","article-title":"Use of antihypertensive medications and mortality of patients with autosomal dominant polycystic kidney disease: A population-based study","volume":"57","author":"Patch","year":"2011","journal-title":"Am. J. Kidney Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1161\/HYPERTENSIONAHA.111.172080","article-title":"Dopamine receptor type 5 in the primary cilia has dual chemo- and mechano-sensory roles","volume":"58","author":"Nauli","year":"2011","journal-title":"Hypertension"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1161\/HYPERTENSIONAHA.110.157727","article-title":"Dopamine receptors","volume":"57","author":"Zeng","year":"2011","journal-title":"Hypertension"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.physiol.65.092101.142243","article-title":"Cardiac hypertrophy: The good, the bad, and the ugly","volume":"65","author":"Frey","year":"2003","journal-title":"Annu. Rev. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1172\/JCI40295","article-title":"Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload","volume":"120","author":"Takeda","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1161\/01.HYP.36.4.489","article-title":"Impact of arterial stiffening on left ventricular structure","volume":"36","author":"Roman","year":"2000","journal-title":"Hypertension"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.1038\/s41467-021-25929-1","article-title":"Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles","volume":"12","author":"Volz","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1903140","DOI":"10.1002\/advs.201903140","article-title":"Proteomic identification reveals the role of ciliary extracellular-like vesicle in cardiovascular function","volume":"7","author":"Mohieldin","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/j.jacc.2015.02.055","article-title":"The unnatural history of the ventricular septal defect: Outcome up to 40 years after surgical closure","volume":"65","author":"Menting","year":"2015","journal-title":"J. Am. Coll. 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