Related Experiment Video
Updated: Jan 25, 2026
Fabrication of 3D Cardiac Microtissue Arrays using Human iPSC-Derived Cardiomyocytes, Cardiac Fibroblasts, and Endothelial Cells
Published on: March 14, 2021
STAT3 and Endothelial Cell-Cardiomyocyte Dialog in Cardiac Remodeling
Fouad A Zouein1, George W Booz2, Raffaele Altara3,4,5
1Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Insights
Signal transducer and activator of transcription 3 (STAT3) is crucial for heart health, mediating communication between endothelial cells and cardiac myocytes. STAT3 regulates inflammation, stress responses, and mitochondrial function, impacting cardiovascular disease and cardiac aging.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Signaling
Background:
- Signal transducer and activator of transcription 3 (STAT3) plays a critical role in cell communication within the heart.
- STAT3 in endothelial cells influences inflammation and cardiac remodeling, particularly in conditions like peripartum cardiomyopathy.
- STAT3 within cardiac myocytes is vital for maintaining endothelial function and vascular integrity during aging and hypertension.
Purpose of the Study:
- To provide an overview of the multifaceted role of STAT3 in the crosstalk between endothelial cells and cardiac myocytes.
- To elucidate STAT3's function as a stress sensor in the heart, responding to oxidative stress and ischemia-reperfusion.
- To explore STAT3's regulation of mitochondrial function, reactive oxygen species (ROS), and calcium signaling in cardiomyocytes.
Main Methods:
- Review of existing literature on STAT3 signaling in cardiovascular contexts.
- Analysis of STAT3's involvement in cellular reprogramming and genetic responses.
- Examination of STAT3's redox regulation and mitochondrial interactions.
Main Results:
- Endothelial STAT3 contributes to inflammation and adverse cardiomyocyte reprogramming in cardiovascular disease.
- Cardiomyocyte STAT3 supports endothelial function and capillary integrity, especially with aging and hypertension.
- STAT3 acts as a cardiac stress sentinel, responding to oxidative stress by inducing protective genes and regulating mitochondrial homeostasis.
Conclusions:
- STAT3 is a central mediator in endothelial-myocyte crosstalk, influencing cardiac structure, function, and disease.
- STAT3's redox-sensitive nature and mitochondrial roles highlight its importance in cellular protection and stress response.
- Further investigation into the integrated roles of STAT3 in both cell types is necessary to understand coordinated cardiac responses to physiological and pathological demands.
Abstract:
This article presents an overview of the central role of STAT3 in the crosstalk between endothelial cells and cardiac myocytes in the heart. Endothelial cell STAT3 has a key role in inflammation that underlies cardiovascular disease and impacts on cardiac structure and function. STAT3 in endothelial cells contributes to adverse cardiomyocyte genetic reprograming, for instance, during peripartum cardiomyopathy. Conversely, cardiomyocyte STAT3 is important for maintaining endothelial cell function and capillary integrity with aging and hypertension. In addition, STAT3 serves as a sentinel for stress in the heart. Recent evidence has revealed that the redox nature of STAT3 is regulated, and STAT3 is responsive to oxidative stress (ischemia-reperfusion) so as to induce protective genes. At the level of the mitochondrion, STAT3 is important in regulating reactive oxygen species (ROS) formation, metabolism, and mitochondrial integrity. STAT3 may also control calcium release from the ER so as to limit its subsequent uptake by mitochondria and the induction of cell death. Under normal conditions, some STAT3 localizes to intercalated discs of cardiomyocytes and serves to transmit pro-fibrotic gene induction signals in the nucleus with increased blood pressure. Further research is needed to understand how the sentinel role of STAT3 in both endothelial cells and cardiomyocytes is integrated in order to coordinate the response of the heart to both physiological and pathological demands.
Related Concept Videos
02:54Nucleosome Remodeling
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
01:40Bone Remodeling
01:31Osteoclasts in Bone Remodeling
01:22Cardiac Output II: Effect of Stroke Volume on Cardiac Output
Preload
Preload refers to the initial elongation of the cardiac myocytes before contraction and is related to the volume of blood filling the heart at the end of diastole, or end-diastolic volume. The...
01:19Cardiac Output I:Effect of Heart Rate on Cardiac Output
Cardiac output (CO) refers to the total amount of blood ejected by one of the ventricles in liters per minute (L/min). In a resting adult, CO ranges from 5 to 6 L/min, adjusting according to the body's metabolic requirements.
Effect of Heart Rate on Cardiac Output
Cardiac output adapts to metabolic demands during stress, physical activity, or illness. The autonomic nervous system regulates heart rate via the sinoatrial node. The parasympathetic nervous system decreases heart...
01:29Cardiac Cycle
During the cardiac cycle, blood flow through the heart is regulated entirely by changing pressure gradients. This sequence of events begins with the heart in a state of total relaxation, known as mid-to-late diastole, during which blood passively flows from...