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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Posttranslational Modifications of the Mineralocorticoid Receptor and Cardiovascular Aging
Yekatarina Gadasheva1, Alexander Nolze1, Claudia Grossmann1
1Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Insights
Cardiovascular aging involves detrimental changes, with the mineralocorticoid receptor (MR) playing a key role. Posttranslational modifications of MR influence its activity, impacting cardiovascular health during aging.
Area of Science:
- Cardiovascular Biology
- Molecular Endocrinology
- Aging Research
Background:
- Cardiovascular aging leads to functional decline and disease, characterized by arterial stiffness, hypertrophy, and inflammation.
- The renin-angiotensin-aldosterone system (RAAS) significantly contributes to cardiovascular remodeling.
- Mineralocorticoid receptor (MR) activity is elevated in aging and cardiovascular disease, independent of aldosterone levels.
Purpose of the Study:
- To review the posttranslational modifications of the mineralocorticoid receptor (MR).
- To elucidate the impact of these modifications on MR function and degradation.
- To explore the implications for cardiovascular aging and associated diseases.
Main Methods:
- Literature review focusing on posttranslational modifications of MR.
- Analysis of studies investigating MR activity, function, and degradation pathways.
- Synthesis of evidence linking MR modifications to cardiovascular aging pathology.
Main Results:
- MR activity increases with aging and cardiovascular disease.
- MR undergoes various posttranslational modifications, including phosphorylation, acetylation, ubiquitination, sumoylation, and stress-induced changes.
- These modifications can modulate MR activity in a ligand-independent manner.
Conclusions:
- Posttranslational modifications are critical regulators of MR activity.
- Understanding these modifications offers potential therapeutic targets for cardiovascular aging.
- Targeting MR modifications may mitigate pathological remodeling and improve cardiovascular outcomes.
Abstract:
During aging, the cardiovascular system is especially prone to a decline in function and to life-expectancy limiting diseases. Cardiovascular aging is associated with increased arterial stiffness and vasoconstriction as well as left ventricular hypertrophy and reduced diastolic function. Pathological changes include endothelial dysfunction, atherosclerosis, fibrosis, hypertrophy, inflammation, and changes in micromilieu with increased production of reactive oxygen and nitrogen species. The renin-angiotensin-aldosterone-system is an important mediator of electrolyte and blood pressure homeostasis and a key contributor to pathological remodeling processes of the cardiovascular system. Its effects are partially conveyed by the mineralocorticoid receptor (MR), a ligand-dependent transcription factor, whose activity increases during aging and cardiovascular diseases without correlating changes of its ligand aldosterone. There is growing evidence that the MR can be enzymatically and non-enzymatically modified and that these modifications contribute to ligand-independent modulation of MR activity. Modifications reported so far include phosphorylation, acetylation, ubiquitination, sumoylation and changes induced by nitrosative and oxidative stress. This review focuses on the different posttranslational modifications of the MR, their impact on MR function and degradation and the possible implications for cardiovascular aging and diseases.
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