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Journal article
Cardiovascular protection in females linked to estrogen-dependent inhibition of arterial stiffening and macrophage MMP12
JCI insight, v 4(1)
10 Jan 2019
PMCID: PMC6485356
PMID: 30626744
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Arterial stiffening is a consequence of aging and a cholesterol-independent risk factor for cardiovascular disease (CVD). Arterial stiffening and CVD show a sex bias, with men more susceptible than premenopausal women. How arterial stiffness and sex interact at a molecular level to confer risk of CVD is not well understood. Here, we used the sexual dimorphism in LDLR-null mice to show that the protective effect of female sex on atherosclerosis is linked to reduced aortic stiffness and reduced expression of matrix metalloproteinase-12 (MMP12) by lesional macrophages. Deletion of MMP12 in LDLR-null mice attenuated the male sex bias for both arterial stiffness and atherosclerosis, and these effects occurred despite high serum cholesterol. Mechanistically, we found that oxidized LDL stimulates secretion of MMP12 in human as well as mouse macrophages. Estrogen antagonizes this effect by downregulating MMP12 expression. Our data support cholesterol-independent causal relationships between estrogen, oxidized LDL-induced secretion of macrophage MMP12, and arterial stiffness that protect against atherosclerosis in females and emphasize that reduced MMP12 functionality can confer atheroprotection to males.
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Details
- Title
- Cardiovascular protection in females linked to estrogen-dependent inhibition of arterial stiffening and macrophage MMP12
- Creators
- Shu-lin Liu - Translational TherapeuticsAnamika Bajpai - Drexel UniversityElizabeth A. Hawthorne - Translational TherapeuticsYongho Bae - Translational TherapeuticsPaola Castagnino - Translational TherapeuticsJames Monslow - University of PennsylvaniaEllen Pure - University of PennsylvaniaKara L. Spiller - Drexel UniversityRichard K. Assoian - Translational Therapeutics
- Publication Details
- JCI insight, v 4(1)
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 11
- Grant note
- Drexel Neuroinflammation and Gender Research Program R01HL130037 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) AG047373; HL130037 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CMMI-1548571 / National Science Foundation Science and Technology Center for Engineering MechanoBiology award
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000455454900005
- Scopus ID
- 2-s2.0-85070661212
- Other Identifier
- 991019168520904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental