Coronary artery disease associated transcription factor TCF21 regulates smooth muscle precursor cells that contribute to the fibrous cap

Nürnberg, Sylvia; Cheng, Karen; Raiesdana, Azad; Kundu, Ramendra K.; Miller, Clint L.; Kim, J.B.; Arora, Kanika; Carcamo-Oribe, Ivan; Xiong, Yuning; Tellakula, Nikhil; Nanda, Vivek; Murthy, Nikitha; Boisvert, William A.; Hedin, Ulf; Perisic, Ljubica; Aldi, Silvia; Maegdefessel, Lars; Pjanic, Milos; Owens, Gary K.; Tallquist, Michelle D.; Quertermous, Thomas

doi:10.1016/j.gdata.2015.05.007

Cited by 22 publications

(25 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Tcf21 has been implicated in fibrous cap formation in coronary atherosclerotic diseases and in focal segmental glomerulosclerosis in kidney . Experiments using cardiovascular smooth muscle cells indicated that Tcf21 directly bound to the promoter regions of Acta2 and Pdgfrb genes and suppressed expression of Acta2 , Pdgfrb , and Col1a1 . From these findings, Tcf21 is considered to be a key molecule that regulates the progression of fibroproliferative diseases and thus could be a common target for antifibrotic therapy in different organs.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, Tcf21 plays critical roles in embryonic development and differentiation of specific types of mesenchymal cells, such as cardiac fibroblasts, renal podocytes, and pulmonary lipofibroblasts . In addition, Tcf21 has been implicated in fibrous cap formation in coronary atherosclerotic diseases and in focal segmental glomerulosclerosis in kidney . Experiments using cardiovascular smooth muscle cells indicated that Tcf21 directly bound to the promoter regions of Acta2 and Pdgfrb genes and suppressed expression of Acta2 , Pdgfrb , and Col1a1 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

et al. 2020

View full text Add to dashboard Cite

Background and Aims Hepatic stellate cells (HSCs), a key player in the progression of liver fibrosis, are activated by various inflammatory stimuli and converted to myofibroblast‐like cells with excessive collagen production. Despite many attempts to suppress activation of HSCs or inhibit collagen production in activated HSCs, their clinical applications have not been established yet. Recently, the deactivation of HSCs has been reported as a mechanism underlying the reversibility of experimental liver fibrosis. In the present study, we sought for deactivation factors of HSCs that induce regression of established liver fibrosis. Approach and Results We identified transcription factor 21 (Tcf21) as one of the transcription factors whose expression was up‐regulated in parallel to the differentiation of fetal HSCs. Expression of Tcf21 in HSCs remarkably decreased during culture‐induced activation in vitro and in murine and human fibrotic liver tissue in vivo. This reduced Tcf21 expression was recovered during the spontaneous regression of murine liver fibrosis. Tcf21 was also examined for its effects by adeno‐associated virus serotype 6‐mediated Tcf21 gene transfer into cultured activated HSCs and mice with carbon tetrachloride‐ or methionine‐choline deficient diet‐induced liver fibrosis. Overexpression of Tcf21 in activated HSCs not only suppressed fibrogenic gene expression but also restored cells, at least in part, to a quiescent phenotype both in vitro and in vivo. These phenotypic changes of HSCs were accompanied by the regression of steatohepatitis and fibrosis and improved hepatic architecture and function. Conclusions Tcf21 has been identified as a deactivation factor of fibrogenic HSCs, providing insight into a treatment strategy for the otherwise intractable liver fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…These studies show that Tcf21 expressing cells migrate into the forming atherosclerotic lesion and contribute to the fibrous cap 187 . Further studies are needed to investigate how lack of TCF21 contributes to lesion size and composition.…”

Section: Examples Of Functional Genomics At Selected Cad Gwas Locimentioning

confidence: 63%

From Loci to Biology

Nürnberg

Zhang

Hand

et al. 2016

Circulation Research

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) have provided a rich collection of ~58 CAD loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are a number of tools that can be employed for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.

show abstract

“…40 GTPase proteins involved in cell growth and differentiation, and high expression of MRAS has been found in heart tissue. 44,45 Rs17609940 is located in the intron region of ANKS1A at chromosome 6. 44,45 Rs17609940 is located in the intron region of ANKS1A at chromosome 6.…”

Section: Discussionmentioning

confidence: 99%

Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients

Pihlstrøm

Mjøen

Mucha

et al. 2019

American Journal of Transplantation

View full text Add to dashboard Cite

CorrespondenceHege Kampen Pihlstrøm Email: hegphi@ous-hf.no Funding information Novartis Pharma AGThere is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible. K E Y W O R D Sbiomarker, clinical research/practice, coronary artery disease, epidemiology, genetics, kidney transplantation/nephrology, risk assessment/risk stratification, translational research/science

show abstract

Coronary artery disease associated transcription factor TCF21 regulates smooth muscle precursor cells that contribute to the fibrous cap

Cited by 22 publications

References 4 publications

A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

From Loci to Biology

Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients

Contact Info

Product

Resources

About