Gender-dependent differential phosphorylation in the ERK signaling pathway is associated with increased MMP2 activity

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Updated: Jun 21, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

Lauren K Ehrlichman1, John W Ford, Karen J Roelofs

  • 1Section of Vascular Surgery, Department of Surgery, Jobst Vascular Research Laboratories, University of Michigan, Ann Arbor, Michigan, USA.

The Journal of Surgical Research
|July 14, 2009
PubMed
Abstract

Insights

Male rats show higher phosphorylated ERK (p-ERK) levels, linked to matrix metalloproteinases (MMPs), potentially explaining gender differences in abdominal aortic aneurysm (AAA) development.

Area of Science:

  • Cardiovascular Biology
  • Molecular Signaling
  • Atherosclerosis Research

Background:

  • Abdominal aortic aneurysms (AAAs) exhibit gender disparities in prevalence and progression.
  • Mitogen-activated protein kinase (MAPK) pathways are implicated as upstream regulators of matrix metalloproteinases (MMPs), key enzymes in AAA pathogenesis.

Purpose of the Study:

  • To investigate the role of MAPK pathways, specifically extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK), and p38, in gender-specific AAA development.
  • To determine if IL-1beta or elastase exposure differentially affects MAPK activation and MMP levels in male and female rat aortic smooth muscle cells (RASMCs).

Main Methods:

  • RASMCs from male and female rats were stimulated with IL-1beta or elastase.
  • Western blotting was used to quantify total and phosphorylated (activated) forms of ERK, JNK, and p38.
  • MMP activity was assessed using zymography.

Main Results:

  • Phosphorylated ERK (p-ERK) levels were significantly higher in males than females post-IL-1beta exposure.
  • Elastase exposure revealed higher total ERK (t-ERK) in females but higher pro-MMP2 levels in males.
  • No significant gender-dependent alterations were observed for p38 or total JNK (t-JNK).

Conclusions:

  • Elevated p-ERK signaling in males, associated with increased MMP activity, may contribute to gender-related differences in AAA formation.
  • These findings highlight the critical role of ERK pathway modulation in AAA pathogenesis and gender disparities.

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