Serum response factor regulates expression of phosphatase and tensin homolog through a microRNA network in vascular smooth muscle cells.

Objective: Serum response factor (SRF) is a critical transcription factor in smooth muscle cells (SMCs) controlling differentiation and proliferation. Our previous work demonstrated that depleting SRF in cultured SMCs decreased expression of SMC markers but increased proliferation and inflammatory mediators. A similar phenotype has been observed in SMCs silenced for phosphatase and tensin homolog (PTEN), suggesting that SRF and PTEN may lie on a common pathway.

SDF-1α induction in mature smooth muscle cells by inactivation of PTEN is a critical mediator of exacerbated injury-induced neointima formation.

Objective: PTEN inactivation selectively in smooth muscle cells (SMC) initiates multiple downstream events driving neointima formation, including SMC cytokine/chemokine production, in particular stromal cell-derived factor-1α (SDF-1α). We investigated the effects of SDF-1α on resident SMC and bone marrow-derived cells and in mediating neointima formation.

Methods And Results: Inducible, SMC-specific PTEN knockout mice (PTEN iKO) were bred to floxed-stop ROSA26-β-galactosidase (βGal) mice to fate-map mature SMC in response to injury; mice received wild-type green fluorescent protein-labeled bone marrow to track recruitment.

Defining the serum 99th percentile in a normal reference population measured by a high-sensitivity cardiac troponin I assay.

Objectives: This study determined the serum 99th percentile reference value for cTnI measured using the high sensitivity Erenna cTnI assay.

Design And Methods: Serum was obtained from healthy adults (n=348); aged 18-76 years of which 147 were males and 201 were females. Nonparametric analysis was performed to determine the 99th percentiles.

Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation.

Aims: Phosphatase and tensin homolog (PTEN) is implicated as a negative regulator of vascular smooth muscle cell (SMC) proliferation and injury-induced vascular remodelling. We tested if selective depletion of PTEN only in SMC is sufficient to promote SMC phenotypic modulation, cytokine production, and enhanced neointima formation.

Methods And Results: Smooth muscle marker expression and induction of pro-inflammatory cytokines were compared in cultured SMC expressing control or PTEN-specific shRNA.

Targeted deletion of PTEN in smooth muscle cells results in vascular remodeling and recruitment of progenitor cells through induction of stromal cell-derived factor-1alpha.

We previously showed that changes in vascular smooth muscle cell (SMC) PTEN/Akt signaling following vascular injury are associated with increased SMC proliferation and neointima formation. In this report, we used a genetic model to deplete PTEN specifically in SMCs by crossing PTEN(LoxP/LoxP) mice to mice expressing Cre recombinase under the control of the SM22alpha promoter. PTEN was downregulated with increases in phosphorylated Akt in major vessels, hearts, and lungs of mutant mice.