BibTex format
@article{Adami:2026:10.1126/scitranslmed.aea2747,
author = {Adami, E and Kim, Y and Zheng, SL and Shvetsov, N and Losert, C and Maatz, H and Barish, S and Venturini, G and Anguita, NL and Shi, Q and Neyazi, M and Beyer, M and Wei, EQ and Adam, A and Suresh, A and Reichart, D and Lindberg, E and Brown, KJ and Strohmenger, V and Saul, D and Gärtner, A and Lee, M and Mach, L and Robertus, JL and Gorham, JM and Haas, J and Liebig, LA and Lippert, C and Meder, B and Myronova, A and Patone, G and Barnett, SN and Ware, JS and de, Robertis F and Pantazis, A and Gummert, J and Viveiros, A and Chen, H and Ruiz-Orera, J and Frey, N and McDonough, BA and Mitchell, RN and Padera, RF and Day, SM and Ho, CY and Lakdawala, NK and Milting, H and Heinig, M and Oudit, GY and Noseda, M and Seidman, JG and Hübner, N and Seidman, CE},
doi = {10.1126/scitranslmed.aea2747},
journal = {Sci Transl Med},
title = {The molecular landscape of hypertrophic cardiomyopathy across disease stages and genotypes.},
url = {http://dx.doi.org/10.1126/scitranslmed.aea2747},
volume = {18},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Hypertrophic cardiomyopathy (HCM) is marked by asymmetric cardiac wall thickening, hypercontractility, diastolic dysfunction, and fibrosis. Pathogenic sarcomere gene variants cause HCM, but comparable abnormalities occur in patients with unexplained disease, albeit with fewer adverse events. To investigate stage- and genotype-specific disease mechanisms, we performed single-nucleus RNA sequencing of cardiac tissues from 47 patients with HCM, spanning obstructive HCM with preserved systolic function and end-stage HCM, and compared them with nonfailing donor and dilated cardiomyopathy hearts. We identified transcriptional programs associated with cardiomyocyte hypertrophy, fibrosis, and vascular remodeling. Pathogenic variant-positive early-stage HCM samples showed reduced cardiomyocyte abundance and expansion of a proarrhythmogenic cardiomyocyte state. We identified proline-rich 16 (PRR16) as a cardiomyocyte growth-associated gene in HCM and validated its increased expression by RNA in situ hybridization and in a human induced pluripotent stem cell-derived cardiomyocyte HCM model. In HCM samples, fibroblast compositional shifts were associated with profibrotic activation and adverse extracellular matrix remodeling, accompanied by reduced collagen IV (COL4A1/COL4A2) expression and ultrastructural basement membrane abnormalities. HCM samples also exhibited extensive vascular alterations, including shifts in endothelial cell subpopulations, reduced pericyte abundance suggestive of microvascular dysfunction, and increased lymphangiogenic vascular endothelial growth factor C signaling. Unsupervised and supervised machine learning approaches distinguished HCM from dilated cardiomyopathy and accurately predicted genotype status in early-stage HCM from cell type-resolved transcriptional profiles, revealing widespread genotype-driven remodeling. Together, our findings uncover multicellular, genotype-associated remodeling programs in HCM, providing insight into mechanisms unde
AU - Adami,E
AU - Kim,Y
AU - Zheng,SL
AU - Shvetsov,N
AU - Losert,C
AU - Maatz,H
AU - Barish,S
AU - Venturini,G
AU - Anguita,NL
AU - Shi,Q
AU - Neyazi,M
AU - Beyer,M
AU - Wei,EQ
AU - Adam,A
AU - Suresh,A
AU - Reichart,D
AU - Lindberg,E
AU - Brown,KJ
AU - Strohmenger,V
AU - Saul,D
AU - Gärtner,A
AU - Lee,M
AU - Mach,L
AU - Robertus,JL
AU - Gorham,JM
AU - Haas,J
AU - Liebig,LA
AU - Lippert,C
AU - Meder,B
AU - Myronova,A
AU - Patone,G
AU - Barnett,SN
AU - Ware,JS
AU - de,Robertis F
AU - Pantazis,A
AU - Gummert,J
AU - Viveiros,A
AU - Chen,H
AU - Ruiz-Orera,J
AU - Frey,N
AU - McDonough,BA
AU - Mitchell,RN
AU - Padera,RF
AU - Day,SM
AU - Ho,CY
AU - Lakdawala,NK
AU - Milting,H
AU - Heinig,M
AU - Oudit,GY
AU - Noseda,M
AU - Seidman,JG
AU - Hübner,N
AU - Seidman,CE
DO - 10.1126/scitranslmed.aea2747
PY - 2026///
TI - The molecular landscape of hypertrophic cardiomyopathy across disease stages and genotypes.
T2 - Sci Transl Med
UR - http://dx.doi.org/10.1126/scitranslmed.aea2747
UR - https://www.ncbi.nlm.nih.gov/pubmed/42748219
VL - 18
ER -