Glucocorticoids: Fuelling the Fire of Atherosclerosis or Therapeutic Extinguishers?

Abstract

Glucocorticoids are steroid hormones with key roles in the regulation of many physiological systems including energy homeostasis and immunity. However, chronic glucocorticoid excess, highlighted in Cushing’s syndrome, is established as being associated with increased cardiovascular disease (CVD) risk. Atherosclerosis is the major cause of CVD, leading to complications including coronary artery disease, myocardial infarction and heart failure. While the associations between glucocorticoid excess and increased prevalence of these complications are well established, the mechanisms underlying the role of glucocorticoids in development of atheroma are unclear. This review aims to better understand the importance of glucocorticoids in atherosclerosis and to dissect their cell-specific effects on key processes (e.g., contractility, remodelling and lesion development). Clinical and pre-clinical studies have shown both athero-protective and pro-atherogenic responses to glucocorticoids, effects dependent upon their multifactorial actions. Evidence indicates regulation of glucocorticoid bioavailability at the vasculature is complex, with local delivery, pre-receptor metabolism, and receptor expression contributing to responses linked to vascular remodelling and inflammation. Further investigations are required to clarify the mechanisms through which endogenous, local glucocorticoid action and systemic glucocorticoid treatment promote/inhibit atherosclerosis. This will provide greater insights into the potential benefit of glucocorticoid targeted approaches in the treatment of cardiovascular disease.

Systemic sclerosis with cerebral infarction and severe stenosis of internal carotid artery and coronary artery: A case report

“…Moreover, the treatment for SSc patients with atherosclerosis is knotty due to the role of glucocorticoid therapy in atherosclerosis being highly controversial. 16 A previous study suggested that low-dose prednisone did not increase the risk of atherosclerosis. 17 Recent studies demonstrated glucocorticoid was associated with a dose-dependent increase in risk of cardiovascular events, even low-dose glucocorticoid increases the risk of cardiovascular disease.…”

“…At present, the treatment mainly focuses on protecting the function of organs and improving the quality of life of patients without specific preventive and treatment measures. Moreover, the treatment for SSc patients with atherosclerosis is knotty due to the role of glucocorticoid therapy in atherosclerosis being highly controversial 16 . A previous study suggested that low‐dose prednisone did not increase the risk of atherosclerosis 17 .…”

An Updated Review of Cardiovascular Events in Giant Cell Arteritis

“…They lead to a direct endothelial cell dysfunction by promoting the production of vasoconstrictors acting on the smooth muscle cells. In addition, some other pre-clinical experimental models suggest an increased accumulation of macrophages in atherosclerotic lesions, with an increased cholesterol esterification [32]. Altogether, long term GC exposure is associated with increased atherosclerosis.…”

“…On one hand, some preclinical studies showed that GC exposure may reduce the recruitment of monocytes and macrophages within the atherosclerotic lesions and reduce the cholesterol accumulation in macrophages. It also results in a reduction of macrophage-induced pro-inflammatory cytokine release limiting the vascular remodeling [32]. On the other hand, GC are also implied in pro-atherogenic mechanisms.…”

Apoptosis Evaluation in Circulating CD34+-Enriched Hematopoietic Stem and Progenitor Cells in Patients with Abnormally Increased Production of Endogenous Glucocorticoids in Course of Cushing’s Syndrome

“…Rarely, Cushing’s Syndrome is caused by primary bilateral macronodular adrenal hyperplasia or primary pigmented nodular adrenocortical disease and its non-pigmented variant: isolated micronodular adrenocortical disease [ 11 ]. Both types of Cushing’s Syndrome (CS) result in excessive adrenal cortisol secretion which binds to the glucocorticoid receptors (GRs), leading to increased morbidity and mortality [ 12 ]. Importantly, modern data suggest that the clinical effects of GC exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism [ 13 , 14 ] and by the GC sensitivity [ 15 ].…”