Caveolin 1 Reduces High Glucose-Induced Hypertrophy and Inflammatory Fibrosis of H9C2 Cardiomyocytes By Inhibiting NF-κB Signaling

Abstract

Background: Cardiac hypertrophy and inflammatory fibrosis are the basic pathological changes of the prevalent microvascular diabetes complication known as diabetic cardiomyopathy (DCM). Previous studies of the Caveolin 1 protein and the lipid raft structures known as caveolae—small invaginations of the plasma membranes of certain cell types (including cardiomyocytes)—have linked this protein to fat metabolism disorders, inflammation, diabetes, and cardiovascular disease. However, there are no reports linking Caveolin 1 to DCM. Here, we show that Caveolin 1 plays a vital role in the hypertrophy and inflammatory fibrosis of H9C2 cardiomyocytes induced by high glucose (HG) via inhibiting the NF-κB signaling.Methods: The H9C2 cardiomyocytes induced by HG were used as the experimental model in this study to explicit the effect of Caveolin 1 on DCM and the underlying mechanisms involved. Unpaired Student’s t test was used for comparison between two groups. For multiple comparisons, data were analyzed by one-way ANOVA with Bonferroni post hoc test multiple comparisons.Results: (1) Exposure of H9C2 cardiomyocytes to HG activated NF-κB signaling and induced the expression of downstream NF-κB target genes including both hypertrophic factors and inflammatory fibrosis factors; (2) Intriguingly, exposure of cardiomyocytes to HG led to decreased Caveolin 1 levels, and this decrease occurred in an HG-exposure-time-dependent manner; (3) Overexpression of Caveolin 1 reduces phosphorylation of p65 and blocks the nuclear accumulation of this NF-κB component in HG-exposed cardiomyocytes, and inhibits transcriptional activation of NF-κB target genes; (4) Knocking down Caveolin 1 exacerbates the HG-induced promotion of the aforementioned NF-κB hypertrophic factors and inflammatory fibrosis factors, all of which have been linked to DCM pathogenesis. Conclusions: Our study supports that Caveolin 1 can protect against hypertrophy and inflammatory fibrosis induced by HG, specifically by suppressing NF-κB signaling activity. Accordingly, some medical implications of our study include that i) Caveolin 1 may protect against the development of DCM and ii) may represent a target for developing therapeutics to protect against this highly prevalent and dangerous microvascular complications of diabetes.