Abstract
Glucocorticoids (GCs) are essential in regulating functions and homeostasis in many biological systems and are extensively used to treat a variety of conditions associated with immune/inflammatory processes. GCs are among the most powerful drugs for the treatment of autoimmune and inflammatory diseases, but their long-term usage is limited by severe adverse effects. For this reason, to envision new therapies devoid of typical GC side effects, research has focused on expanding the knowledge of cellular and molecular effects of GCs. GC-induced leucine zipper (GILZ) is a GC-target protein shown to mediate several actions of GCs, including inhibition of the NF-κB and MAPK pathways. GILZ expression is not restricted to immune cells, and it has been shown to play a regulatory role in many organs and tissues, including the cardiovascular system. Research on the role of GILZ on endothelial cells has demonstrated its ability to modulate the inflammatory cascade, resulting in a downregulation of cytokines, chemokines, and cellular adhesion molecules. GILZ also has the capacity to protect myocardial cells, as its deletion makes the heart, after a deleterious stimulus, more susceptible to apoptosis, immune cell infiltration, hypertrophy, and impaired function. Despite these advances, we have only just begun to appreciate the relevance of GILZ in cardiovascular homeostasis and dysfunction. This review summarizes the current understanding of the role of GILZ in modulating biological processes relevant to cardiovascular biology.
Highlights
Stress is a well-recognized factor in cardiovascular diseases [1]
A myriad of studies have confirmed the role of biological stress in cardiovascular disease, and have linked cardiovascular risk factors to chronic stress
Among inflammation-regulating genes with significantly altered expression, the analysis revealed an enhanced expression of GC-induced leucine zipper (GILZ) [86]
Summary
Stress is a well-recognized factor in cardiovascular diseases [1]. A myriad of studies have confirmed the role of biological stress (oxidative, hemodynamic, metabolic, etc.) in cardiovascular disease, and have linked cardiovascular risk factors to chronic stress. Chronic exposure to stressors causes endocrine and immune dysregulation that sustains low-grade inflammation, which evolves to become systemic and detrimental. The endocrine system responses to stress by producing and secreting hormones that regulate a wide range of biological functions, including growth and development, sexual reproduction, metabolism, heart rate, blood pressure, sleeping and waking cycles, etc. GCs are called “stress hormones”, and their increased secretion upon anxiety and severe injury is desirable, but when chronically elevated, circulating GCs are linked to adverse cardiovascular outcomes [7,8]. The role of GCs in maturation of the fetal heart further supports the importance of GC signaling in cardiovascular biology [9,10]
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