Leptin and vascular smooth muscle cells

Mariella Trovati, Gabriella Doronzo, Cristina Barale, Claudia Vaccheris, Isabella Russo, Franco Cavalot

Research output: Contribution to journalArticle

Abstract

This review concerns the influence of leptin on vascular smooth muscle cells (VSMC). VSMC express different isoforms of the leptin receptor (Ob-R) able to activate a wide range of intracellular signalling pathways, mediating many relevant biological actions. In particular, leptin promotes processes deeply involved in atherogenesis, such as VSMC migration, hypertrophy, proliferation, osteogenic differentiation and metalloproteinase expression. The intracellular signalling molecules involved are JAK/STAT, PI3K/Akt, ERK 1/2, p38 MAPK, mTOR, and RhoA/ROCK. Some of these leptin actions are particularly evident in stretching conditions; others are mediated by the NAD(P)H-induced increase of Reactive Oxygen Species. A leptin-induced activation of angiotensin and endothelin systems, with up-regulation of the synthesis of the two hormones and of their receptors, has also been demonstrated. Other studies, however, showed that leptin increases in VSMC the nitric oxide production by activating the inducible nitric oxide synthase, and, via nitric oxide, exerts a vasodilating effect and impairs the proliferative and vasoconstricting actions of angiotensin II. Both the potentially harmful and the potentially beneficial effects exerted by leptin in VSMC are lost in VSMC from animal models of genetically determined leptinresistance. Cultured VSMC from leptin-resistant animals are also resistant to insulin and to nitric oxide. It is not known, however, whether in human obesity, a condition characterized by hypothalamic leptin resistance and by compensatory hyperleptinemia, VSMC are sensitive or resistant to leptin: only in the first case the predictive role of circulating leptin on cardiovascular events could support a pathogenetic influence of the hormone on atherosclerosis.

Original languageEnglish
Pages (from-to)625-634
Number of pages10
JournalCurrent Pharmaceutical Design
Volume20
Issue number4
Publication statusPublished - 2014

Keywords

  • Atherosclerosis
  • Insulin resistance
  • Leptin
  • Leptin resistance
  • Nitric oxide
  • Obesity
  • Restenosis
  • Vascular calcification
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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  • Cite this

    Trovati, M., Doronzo, G., Barale, C., Vaccheris, C., Russo, I., & Cavalot, F. (2014). Leptin and vascular smooth muscle cells. Current Pharmaceutical Design, 20(4), 625-634.