{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:30:57Z","timestamp":1760059857202,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Magdi Yacoub Institute","award":["MYI0050"],"award-info":[{"award-number":["MYI0050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>(1) Background: The sophisticated function of the aortic root relies on the coordinated movement of its constituent components. This study examines the extracellular components of the interleaflet triangles (ILTs) and characterises the cells that are present within this region of the aortic root. (2) Methods: A total of 10 human aortic valves and 6 porcine aortic valves were processed for immunohistochemical staining, scanning, and transmission electron microscopy. (3) Results: The three ILTs differed in size and macroscopic appearance. Each triangle comprised up to five distinct layers of tissue: an innermost endothelial layer, an inner elastin-rich layer, a thicker outer layer comprising densely packed layers of collagen and glycosaminoglycans, and an outer layer of intermingled myocardial and adipose tissue. A band of cells near the luminal surfaces of all ILTs expressed smooth muscle cell \u03b1-actin with variable expression of smooth muscle myosin heavy chain. In all the ILTs, there was evidence of neurofilament staining, indicating the presence of nerve fibres. (4) Conclusions: Each ILT is unique in its structure and organisation, with differing amounts of elastin and collagen, as well as myocardial, adipose, and fibrous content. The ILTs contain multiple cell types in varying abundance. Functional studies are required to determine the role of the different cells and their organisation in contributing to the sophisticated, dynamic behaviour of the aortic root.<\/jats:p>","DOI":"10.3390\/biology14070863","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T15:48:22Z","timestamp":1752680902000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular and Matrix Organisation of the Human Aortic Valve Interleaflet Triangles"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-2150","authenticated-orcid":false,"given":"Najma","family":"Latif","sequence":"first","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, London UB9 6JH, UK"},{"name":"ICTEM Building, National Heart & Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9331-3046","authenticated-orcid":false,"given":"Padmini","family":"Sarathchandra","sequence":"additional","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, London UB9 6JH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albaraa","family":"Al-Holy","sequence":"additional","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, London UB9 6JH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanida","family":"Vaz","sequence":"additional","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, London UB9 6JH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-1075","authenticated-orcid":false,"given":"Adrian H.","family":"Chester","sequence":"additional","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, London UB9 6JH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-8245","authenticated-orcid":false,"given":"Magdi H.","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, London UB9 6JH, UK"},{"name":"ICTEM Building, National Heart & Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/S0003-4975(99)00745-6","article-title":"The aortic outflow and root: A tale of dynamism and crosstalk","volume":"68","author":"Yacoub","year":"1999","journal-title":"Ann. Thorac. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/S0022-5223(95)70246-6","article-title":"Regulation of the aortic valve opening. In vivo dynamic measurement of aortic valve orifice area","volume":"110","author":"Higashidate","year":"1995","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"II54","DOI":"10.1161\/circ.100.suppl_2.Ii-54","article-title":"Deformational dynamics of the aortic root: Modes and physiologic determinants","volume":"100","author":"Dagum","year":"1999","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1152\/jappl.1971.30.5.611","article-title":"Size and motion of the mitral valve annulus in anesthetized intact dogs","volume":"30","author":"Tsakiris","year":"1971","journal-title":"J. Appl. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1152\/physrev.00038.2022","article-title":"Multiscale structure and function of the aortic valve apparatus","volume":"104","author":"Sabry","year":"2024","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0003-4975(94)00893-C","article-title":"The forgotten interleaflet triangles: A review of the surgical anatomy of the aortic valve","volume":"59","author":"Sutton","year":"1995","journal-title":"Ann. Thorac. Surg."},{"key":"ref_7","first-page":"52","article-title":"The living aortic valve: From molecules to function","volume":"2014","author":"Chester","year":"2014","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0140-6736(10)60828-8","article-title":"Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: A randomised controlled trial","volume":"376","author":"Eryigit","year":"2010","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Latif, N., Quillon, A., Sarathchandra, P., McCormack, A., Lozanoski, A., Yacoub, M.H., and Chester, A.H. (2015). Modulation of human valve interstitial cell phenotype and function using a fibroblast growth factor 2 formulation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127844"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1093\/eurheartj\/eht547","article-title":"Expression of smooth muscle cell markers and co-activators in calcified aortic valves","volume":"36","author":"Latif","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1540-8191.2001.tb01159.x","article-title":"Biological mechanisms influencing the function of the aortic root","volume":"17","author":"Misfeld","year":"2002","journal-title":"J. Card. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1093\/ejcts\/ezaa019","article-title":"Long-term adaptive versus maladaptive remodelling of the pulmonary autograft after the Ross operation","volume":"57","author":"Yacoub","year":"2020","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.jacc.2008.11.056","article-title":"Endothelium-dependent regulation of the mechanical properties of aortic valve cusps","volume":"53","author":"Balachandran","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.yjmcc.2008.03.014","article-title":"Localisation and function of nerves in the aortic root","volume":"44","author":"Chester","year":"2008","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_15","first-page":"250","article-title":"Receptor-mediated contraction of aortic valve leaflets","volume":"9","author":"Chester","year":"2000","journal-title":"J. Heart Valve Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1253\/circj.CJ-20-0938","article-title":"Normative Aortic Valvar Measurements in Adults Using Cardiac Computed Tomography\u2015A Potential Guide to Further Sophisticate Aortic Valve-Sparing Surgery","volume":"85","author":"Izawa","year":"2021","journal-title":"Circ. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/ejcts\/ezv059","article-title":"A geometric approach to aortic root surgical anatomy","volume":"49","author":"Contino","year":"2016","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.athoracsur.2014.12.034","article-title":"Surgical anatomy of the aortic annulus: Landmarks for external annuloplasty in aortic valve repair","volume":"99","author":"Khelil","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1114\/1.122","article-title":"Stress variations in the human aortic root and valve: The role of anatomic asymmetry","volume":"26","author":"Grande","year":"1998","journal-title":"Ann. Biomed. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0022-5223(95)70396-9","article-title":"Repair of the aortic valve in patients with aortic insufficiency and aortic root aneurysm","volume":"109","author":"David","year":"1995","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/joa.12713","article-title":"Development and maturation of the fibrous components of the arterial roots in the mouse heart","volume":"232","author":"Richardson","year":"2018","journal-title":"J. Anat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"dev151944","DOI":"10.1242\/dev.151944","article-title":"Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve","volume":"145","author":"Odelin","year":"2018","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jbiomech.2018.04.037","article-title":"Biomechanical characterization of the native porcine aortic root","volume":"74","author":"Bechsgaard","year":"2018","journal-title":"J. Biomech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s10554-011-9838-x","article-title":"Aortic root dimension changes during systole and diastole: Evaluation with ECG-gated multidetector row computed tomography","volume":"27","author":"Budde","year":"2011","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_25","first-page":"1307","article-title":"Does the aortic annulus undergo conformational change throughout the cardiac cycle? A systematic review","volume":"16","author":"Tuncay","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"H756","DOI":"10.1152\/ajpheart.00900.2008","article-title":"Elevated cyclic stretch alters matrix remodeling in aortic valve cusps: Implications for degenerative aortic valve disease","volume":"296","author":"Balachandran","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_27","first-page":"798","article-title":"Specific regional and directional contractile responses of aortic cusp tissue","volume":"13","author":"Kershaw","year":"2004","journal-title":"J. Heart Valve Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fedele, L., and Brand, T. (2020). The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction. J. Cardiovasc. Dev. Dis., 7.","DOI":"10.3390\/jcdd7040054"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s12055-023-01645-x","article-title":"An overview of aortic valve anatomy: The current understanding","volume":"39","author":"Lansakara","year":"2023","journal-title":"Indian J. Thorac. Cardiovasc. Surg."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/7\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:10:51Z","timestamp":1760033451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/7\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biology14070863"],"URL":"https:\/\/doi.org\/10.3390\/biology14070863","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}