Dataset Information

Single Cell RNA Sequencing of C57BL6 mouse whole aortas after 8 weeks of L-NAME treatment

ABSTRACT: Humans with a heterozygous loss-of-function SERPINE1 variant exhibit protection against biological aging and cardiometabolic dysfunction. Here, we reverse engineered a mouse model mimicking the human mutation (Serpine1TA700/+) and compared cardiovascular responses with wild-type littermates. Under L-NG-Nitro-arginine methyl ester (L-NAME)-induced vascular stress, Serpine1TA700/+ mice exhibited protection from systolic hypertension (SBP), preserved left ventricular diastolic function, and diminished aortic pulse wave velocity (PWV) compared to controls. Single cell transcriptomic analyses of Serpine1TA700/+ aortas, revealed a vascular-protective mechanism that involves the downregulation of extracellular matrix regulators Ccn1 and Itgb1.

ORGANISM(S): Mus musculus

PROVIDER: GSE297835 | GEO | 2025/09/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Effects of the matricellular protein CCN1 on macrophage inflammatory gene expression was tested in a macrophage cell line I-13.35. CCN1 (CYR61) is a matricellular protein that is highly expressed at sites of inflammation and wound repair. In these contexts, CCN1 can modify the activities of specific cytokines, enabling TNF-alpha to be cytotoxic without blocking NFkB activity and enhancing the apoptotic activity of FasL and TRAIL. Here we show that CCN1 supports the adhesion of macrophages through integrin alphaMbeta2 and syndecan-4, activates NFkB-mediated transcription, and induces a pro-inflammatory genetic program characteristic of classically activated M1 macrophages that participates in Th1 responses. The effects of CCN1 include upregulation of cytokines (TNFa, IL-1a, IL-1b, IL-6, IL-12b), chemokines (MIP-1a, MCP-3, Gro1, Gro2, IP-10), regulators of oxidative stress and complement (iNOS, C3), and downregulation of specific receptors (TLR4, IL-10rb) and anti-inflammatory factors (TGF-b1). CCN1 regulates this genetic program through at least two distinct mechanisms: an immediate-early response resulting from direct activation of NFkB by CCN1, leading to the synthesis of cytokines including TNFa and IP-10; and a delayed response resulting from CCN1-induced TNFa, which acts as an autocrine/paracrine mediator to activate the expression of other cytokines including IL-1b and IL-6. These results identify CCN1 as a novel component of the extracellular matrix that activates pro-inflammatory genes in macrophages, implicating its role in regulating macrophage function during inflammation. Macrophage cell line I-13.35 (from Tlr4-defective C3H/HeJ) was treated with purified recombinant CCN1 protein for 6 hr. Total RNA was isolated, converted to cRNA probes, and hybridized to a oligonucleotide array representing 113 murine inflammation-related genes (from SA Biosciences at www.sabiosciences.com, Cat. Number OMM-011.) The array is a nylon membrane based DNA microarray on which 60-mer oligonucleotides probes were printed. Gene expression profile of resting cells incubated in serum-free medium (containing albumin, BSA) was used as a control for basal levels of gene expression.

Dataset Information

Single Cell RNA Sequencing of C57BL6 mouse whole aortas after 8 weeks of L-NAME treatment

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets