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Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE205091 | GEO | 2022/06/02

REPOSITORIES: GEO

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Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure

Project description:Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and a variety of age-related diseases in men, but causal and mechanistic relationships have yet to be established. Here it is shown that mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including a progressive decline in cardiac function. Accelerated cardiac dysfunction and fibrosis were also observed in younger mice subjected to a pressure-overload model of heart failure. Bone marrow-derived, cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic and less inflammatory phenotype. Treatment with a TGFb1 neutralizing antibody led to greater amelioration of heart failure in mice reconstituted with mLOY compared to wild-type bone marrow. Consistent with these data, a prospective study in men revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure-associated mortality. Together, these results indicate that hematopoietic mLOY contributes to heart failure in men.

2022-08-01 | GSE204732 | GEO

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_WholeBloodNeutrophils]

2022-06-02 | GSE205090 | GEO

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_HeartNeutrophils]

2022-06-02 | GSE205089 | GEO

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_HeartMacrophages]

2022-06-02 | GSE205088 | GEO

Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality.

Project description:Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including reduced cardiac function. Cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic phenotype, and treatment with a transforming growth factor β1-neutralizing antibody ameliorated cardiac dysfunction in mLOY mice. A prospective study revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure-associated mortality. Together, these results indicate that hematopoietic mLOY causally contributes to fibrosis, cardiac dysfunction, and mortality in men.

| S-EPMC9437978 | biostudies-literature

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure

Project description:Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure

| PRJNA842029 | ENA

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure.

Project description:Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure.

| PRJNA843697 | ENA

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_HeartMacrophages]

Project description:Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_HeartMacrophages]

| PRJNA843704 | ENA

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_HeartNeutrophils]

Project description:Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_HeartNeutrophils]

| PRJNA843703 | ENA

Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_WholeBloodNeutrophils]

Project description:Hematopoietic Loss of Y Chromosome Leads to Cardiac Fibrosis and Dysfunction and is Associated with Death due to Heart Failure [bulkRNAseq_WholeBloodNeutrophils]

| PRJNA843702 | ENA

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