Citations 3
CDCP1 Deletion Protects Against Pressure Overload-Induced Cardiac Dysfunction and Fibrosis in Mice
Pereira, Naveen, Ghazal, Rachad, wang, Min, Cao, Jenny Jia Ling, Wang, Li , Sherman, William , John, August, Vyas, Hridyanshu , Roos, Carolyn, Huang, Runqing, Ördög, Tamás , Trussoni, Christy, Lim, Do Young , Sinagra, Gianfranco, Weinshilboum, Richard M. , Liu, Duan , Lambert, Laura , Miller, Jordan , Tschumperlin, Daniel, Srinivas, Akshatha N. , Sherman, Will A , Ordog, Tamas , Wang, Chen , Baker, Darren J , Weinshilboum, Richard M. , Liu, Duan , Lambert, Laura J, Pereira, Naveen, Ghazal, Rachad , Cao, Jenny Jia Ling , Wang, Li, Marín-Goñi, Irene , Wang, Chen , Trussoni, Christy E. , Baker, Darren J. , Sinagra, Gianfranco , Tschumperlin, Daniel J.
No container title available | May 8, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Human genomic studies link reduced CUB domain-containing protein 1 (CDCP1) expression with myocardial recovery in heart failure. While CDCP1 regulates cardiac fibroblast proliferation in vitro, it’s in vivo role in cardiac fibrosis remains unclear. Using a Cdcp1 -knockout (KO) angiotensin II/phenylephrine mouse model, we show that Cdcp1 deletion reduces echocardiographic left ventricular mass, histologic cardiac fibrosis, and pro-fibrotic gene expression, along with decreased fibroblast activation and inflammatory markers. Spatial transcriptomics identified a pressure overload–expanded fibroblast subpopulation enriched for growth factor and TGF-β signaling (FB5), which was markedly attenuated in Cdcp1 -KO hearts, alongside reduction of a pro-inflammatory cardiomyocyte subtype (CM4). Complementary studies in human ventricular fibroblasts demonstrate that CDCP1 knockdown reduced extracellular matrix gene expression and collagen I deposition. These findings establish CDCP1 as a regulator of cardiac fibrotic remodeling in vivo and open avenues for its further investigation as a potential therapeutic target.
Novel association of NAV3 with dilated cardiomyopathy and its role in cardiac fibrosis
wang, Min, Ghazal, Rachad , Srinivas, Akshatha N. , Nguyen, Thanh Thanh L. , Murthy, Vishakantha , McNamara, D., Skime, Michelle , Batzler, Anthony , Jenkins, Gregory D. , Barlera, Simona, Mestroni, Luisa, Merlo, Marco, Pinet, Florence, Krejčí, Jan, Chaloupka, Anna , Groote, Pascal. De, Weinshilboum, RM, Tschumperlin, Daniel J. , Liu, Duan , Pereira, Naveen, McNamara, Dennis M. , Nguyen, Thanh Thanh L. , Wang, Min , Ghazal, Rachad , Wang, Min , McNamara, Dennis M , Skime, Michelle K , Pileggi, Silvana , Mestroni, Luisa , Pinet, Florence , Krejčí, Jan , Chaloupka, Anna , de Groote, Pascal , Weinshilboum, Richard M. , Tschumperlin, Daniel J , Liu, Duan , Pereira, Naveen L , Pileggi, Silvana , Mestroni, Luisa , Merlo, Marco , Pinet, F , Krejčí, Jan , Groote, Pascal de
American Journal of Physiology-Heart and Circulatory Physiology | January 29, 2026 | Volume: 330 | Issue: 3 | Pages: H686-H696
This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.
Longitudinal Peripheral Blood Transcriptomics Reveal Novel Signatures During Cardiac Allograft Rejection
Ghazal, Rachad , Wang, Min, Cao, Jenny Jia Ling, Vyas, Hridyanshu , Liu, Duan , Nair, Asha , Wang, Li , Yip, D., Patel, Parag C., Steidley, D. Eric , Hardaway, Brian , Clavell, Alfredo L., Kushwaha, Sudhir S. , Eisen, Howard J., Pereira, Naveen, Srinivas, Akshatha N. , Steidley, David E, Hardaway, Brian W, Pereira, Naveen L , Liu, Duan , Ghazal, Rachad , Srinivas, Akshatha N., Smith, Byron H. , Yip, Daniel , Patel, Parag C. , Clavell, Alfredo L. , Park, Walter D. , Stegall, Mark D. , Eisen, Howard J.
Transplantation Direct | January 20, 2026 | Volume: 12 | Issue: 2 | Pages: e1882
Background. Acute cellular rejection (ACR) remains a major cause of morbidity after heart transplantation despite advances in immunosuppression. Whole genome transcriptomic profiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive, longitudinal biomarker assessments capable of capturing the temporal dynamics of rejection biology remain scarce. Methods. RNA sequencing of peripheral blood from heart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assess gene-based prediction of ACR. Results. A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning–based classifier, DYNLL1 and SERF2 were identified as ACR predictive genes, and achieved a cross-validated area under the receiver operating characteristic curve of 0.63. Conclusions. Peripheral blood transcriptomics identify dynamic temporal responses in ACR including T- and B-cell pathways with potential ACR predictive genes that warrant further investigation.