Dataset Information

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE^-/- Mice Against Leptin-Induced Atherosclerosis.

ABSTRACT:

Objective

Hyperleptinemia, hallmark of obesity, is a putative pathophysiologic trigger for atherosclerosis. We previously reported a stimulatory effect of leptin on TSP-1 (thrombospondin-1) expression, a proatherogenic matricellular protein implicated in atherogenesis. However, a causal role of TSP-1 in leptin-driven atherosclerosis remains unknown. Approach and Results: Seventeen-weeks-old ApoE^-/- and TSP-1^-/-/ApoE^-/- double knockout mice, on normocholesterolemic diet, were treated with or without murine recombinant leptin (5 µg/g bwt, IP) once daily for 3 weeks. Using aortic root morphometry and en face lesion assay, we found that TSP-1 deletion abrogated leptin-stimulated lipid-filled lesion burden, plaque area, and collagen accumulation in aortic roots of ApoE^-/- mice, shown via Oil red O, hematoxylin and eosin, and Masson trichrome staining, respectively. Immunofluorescence microscopy of aortic roots showed that TSP-1 deficiency blocked leptin-induced inflammatory and smooth muscle cell abundance as well as cellular proliferation in ApoE^-/- mice. Moreover, these effects were concomitant to changes in VLDL (very low-density lipoprotein)-triglyceride and HDL (high-density lipoprotein)-cholesterol levels. Immunoblotting further revealed reduced vimentin and pCREB (phospho-cyclic AMP response element-binding protein) accompanied with augmented smooth muscle-myosin heavy chain expression in aortic vessels of leptin-treated double knockout versus leptin-treated ApoE^-/-; also confirmed in aortic smooth muscle cells from the mice genotypes, incubated ± leptin in vitro. Finally, TSP-1 deletion impeded plaque burden in leptin-treated ApoE^-/- on western diet, independent of plasma lipid alterations.

Conclusions

The present study provides evidence for a protective effect of TSP-1 deletion on leptin-stimulated atherogenesis. Our findings suggest a regulatory role of TSP-1 on leptin-induced vascular smooth muscle cell phenotypic transition and inflammatory lesion invasion. Collectively, these results underscore TSP-1 as a potential target of leptin-induced vasculopathy.

SUBMITTER: Ganguly R

PROVIDER: S-EPMC8105272 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE<sup>-/-</sup> Mice Against Leptin-Induced Atherosclerosis.

Ganguly Rituparna R Khanal Saugat S Mathias Amy A Gupta Shreya S Lallo Jason J Sahu Soumyadip S Ohanyan Vahagn V Patel Aakaash A Storm Kyle K Datta Sujay S Raman Priya P

Arteriosclerosis, thrombosis, and vascular biology 20201217 2

<h4>Objective</h4>Hyperleptinemia, hallmark of obesity, is a putative pathophysiologic trigger for atherosclerosis. We previously reported a stimulatory effect of leptin on TSP-1 (thrombospondin-1) expression, a proatherogenic matricellular protein implicated in atherogenesis. However, a causal role of TSP-1 in leptin-driven atherosclerosis remains unknown. Approach and Results: Seventeen-weeks-old ApoE<sup>-/-</sup> and TSP-1<sup>-/-</sup>/ApoE<sup>-/-</sup> double knockout mice, on normocholes ...[more]

PMID: 33327743

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Dataset Information

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE^-/- Mice Against Leptin-Induced Atherosclerosis.

Objective

Conclusions

Publications

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE<sup>-/-</sup> Mice Against Leptin-Induced Atherosclerosis.

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Dataset Information

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE-/- Mice Against Leptin-Induced Atherosclerosis.

Objective

Conclusions

Publications

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE<sup>-/-</sup> Mice Against Leptin-Induced Atherosclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

TSP-1 (Thrombospondin-1) Deficiency Protects ApoE^-/- Mice Against Leptin-Induced Atherosclerosis.