Monday, February 16, 2026 2/16/2026

The novel smooth muscle-specific lncRNA CARMN is a critical regulator of smooth muscle phenotype

Award Number: R01HL149995
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/20/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

Group Awards By:

View Award Description

The novel smooth muscle-specific lncRNA CARMN is a critical regulator of smooth muscle phenotype - PROJECT SUMMARY Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile to a proliferative phenotype, plays a causal role in many human occlusive vascular diseases. However, the key factors critical for the event are far from completely identified. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are critical for gene expression but VSMC-specific lncRNAs remain ill-defined. In an effort to identify lncRNAs with a role in regulating VSMC phenotype, we utilized publicly available RNA-seq and ChIP-seq data sets that are generated from different cells/tissues to identify VSMC-enriched lncRNAs. This unbiased analysis revealed that the lncRNA CARMN is specifically expressed in VSMCs. Correlation analysis revealed that SM-specific expression of CARMN is not only correlated with a set of well-known SM-contractile markers, but also with serum response factor (SRF) and its cardiac/SM-specific cofactor myocardin (MYOCD). SRF/MYOCD is a transcriptional complex that plays a critical role in regulating SM-specific contractile gene expression, through binding to the CArG boxes within these genes. Bioinformatic analysis identified 2 evolutionarily conserved CArG boxes within CARMN gene locus and our exciting preliminary data further demonstrated that CARMN expression is SRF/MYOCD- dependent. Furthermore, we found that CARMN is down-regulated during VSMC phenotypic switching in vivo and in vitro. More importantly, depletion of CARMN inhibits while overexpression of CARMN promotes the contractile phenotype of VSMCs. Remarkably, our exciting preliminary data further showed that CARMN acts as a transcriptional activator by binding to MYOCD but also synergistically enhancing MYOCD-mediated transactivation on SM-specific genes including CARMN itself. Therefore, we hypothesize that SRF/MYOCD drives SM-specific lncRNA CARMN expression and that CARMN plays a critical role in maintaining the contractile state of VSMCs through a positive feedback mechanism by binding to MYOCD. Three aims are proposed to test this novel hypothesis. In Aim 1, we will determine the regulatory mechanism by which CARMN specifically expresses in VSMCs by using our novel CARMN knock-in reporter mice, ChIP assay, mutagenesis in vitro and CRISPR-Cas9 genome editing of CArG box in vivo. In Aim 2, we will define the functional role of CARMN in VSMCs by using our novel inducible SM-specific CARMN KO mice and rat carotid artery balloon injury model. In Aim 3, we will explore the mechanism of CARMN's action in VSMCs by assessing the physical and functional binding of CARMN with MYOCD. Completion of these studies will provide novel insights into the mechanisms controlling VSMC phenotypic plasticity and identify the novel SM-specific lncRNA CARMN for treating many proliferative vascular diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$277 )
2025	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	4	4/30/2025	NON-COMPETING CONTINUATION	-$277
														Subtotal = -$277

Issue Date FY: 2023 ( Subtotal = $500,500 )
2023	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	001	4	3/10/2023	NON-COMPETING CONTINUATION	$50,051
2023	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	4	1/10/2023	NON-COMPETING CONTINUATION	$450,449
														Subtotal = $500,500

Issue Date FY: 2022 ( Subtotal = $500,500 )
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	3	12/23/2021	NON-COMPETING CONTINUATION	$450,448
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	001	3	6/9/2022	NON-COMPETING CONTINUATION	$50,052
														Subtotal = $500,500

Issue Date FY: 2021 ( Subtotal = $500,500 )
2021	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	001	2	5/24/2021	NON-COMPETING CONTINUATION	$50,052
2021	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	2	1/9/2021	NON-COMPETING CONTINUATION	$450,448
														Subtotal = $500,500

Issue Date FY: 2020 ( Subtotal = $498,063 )
2020	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	001	1	2/27/2020	NEW	$813
2020	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	1	1/20/2020	NEW	$497,250
														Subtotal = $498,063

Grand Total All Awards = $1,999,286

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The novel smooth muscle-specific lncRNA CARMN is a critical regulator of smooth muscle phenotype

Award Number: R01HL149995

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/20/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer