[Frontiers in Bioscience 17, 1917-1930, January 1, 2012]

Nuclear receptor control of opposing macrophage phenotypes in cardiovascular disease

Ryan A. Frieler1,2, Saiprasad Ramnarayanan1, Richard M. Mortensen1,2,3

1Department of Molecular and Integrative Physiology, 2Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, 3Internal Medicine, Metabolism, Endocrinology, and Diabetes Division, University of Michigan Medical School, Ann Arbor, MI 48109


1. Abstract
2. Introduction
3. Nuclear receptor control of macrophage activation
3.1. Regulation of macrophage activation by PPARs
3.2. Mineralocorticoid receptor activates proinflammatory macrophage function
3.3. Interaction of nuclear receptors and cytokines
4. Alternatively activated macrophage phenotypes in cardiovascular disease
4.1. Cardiac inflammation, hypertrophy and fibrosis
4.2. Atherosclerosis
4.3. Stroke
5. Heme oxygenase-1 in alternatively activated macrophages
5.1. Atherosclerosis
5.2. Alveolar macrophages and pulmonary hypertension
6. Strategies to study macrophage polarization in disease
7. Summary and perspectives
8. Acknowledgements
9. References


Macrophages have important physiological roles and display a high degree of heterogeneous phenotypes in response to a variety of stimuli. In particular, the spectrum of alternatively activated macrophages has been a focus because many lines of evidence indicate a cardioprotective role for this macrophage phenotype. This phenotype is controlled in part by opposing nuclear transcription factors including the PPARs that stimulate alternative activation and the recently recognized role of the mineralocorticoid receptor in stimulating classically activated macrophages. This review highlights some of the recent findings involving alternatively activated macrophages and these nuclear receptors in cardiovascular disease.