Cardiac Hypertrophy and Related Dysfunctions in Cushing Syndrome Patients—Literature Review

Kanzaki, Akinori; Kadoya, Masumi; Katayama, Satoru; Koyama, Hideki

doi:10.3390/jcm11237035

Cited by 5 publications

(3 citation statements)

References 125 publications

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“…Additionally, conditions such as Cushing syndrome, circadian disruption, and cardiomyopathy, which are associated with increased myocardial fibrosis [ 48 – 50 ], were found to be relevant to the up-regulated pathways in IR-fibrosis HOs. Cortisol is also experimentally shown to induce cardiomyocyte hypertrophy [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Song,

Choi,

et al. 2024

Cell Death Dis

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Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Song,

Choi,

et al. 2024

Cell Death Dis

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“…In our case, the patient's CMR imaging showed typical features of cardiac geometry, function, and fibrosis, in accordance with previous reports. 4 The underlying mechanisms may be the enhanced responsiveness to angiotensin II and activation of the mineralocorticoid receptor in direct response to cortisol excess. 5 Our patient responded well to the therapy of conventional anti-HF medication of sacubitril/valsartan, metoprolol, and diuretic, once mifepristone was added.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cushing's syndrome presenting as non‐atherosclerotic myocardial infarction and heart failure

Li,

He,

Feng

et al. 2023

ESC Heart Failure

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Cushing's syndrome is a rare cause of myocardial infarction and heart failure. Herein, we report a female patient who presented acute myocardial infarction and heart failure with reduced ejection fraction. The patient was found to have hypercortisolism secondary to adrenocortical adenoma and responded well to therapy. This case underlines the effects of hypercortisolism on the cardiovascular system. The clinical presentation of this patient is unique because non‐atherosclerotic myocardial infarction is rarely reported in Cushing's syndrome patients.

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Cardiac magnetic resonance reveals biventricular impairment in Cushing’s syndrome: a multicentre case-control study

Feola,

Cozzolino,

De Alcubierre

et al. 2024

Endocrine

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Purpose Cushing’s syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. Methods This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. Results Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. Conclusion CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors.

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Cardiac Hypertrophy and Related Dysfunctions in Cushing Syndrome Patients—Literature Review

Cited by 5 publications

References 125 publications

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids

Cushing's syndrome presenting as non‐atherosclerotic myocardial infarction and heart failure

Cardiac magnetic resonance reveals biventricular impairment in Cushing’s syndrome: a multicentre case-control study

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