Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease.

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disability. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes.

Exogenous Transforming Growth Factor-β1 and Its Helminth-Derived Mimic Attenuate the Heart's Inflammatory Response to Ischemic Injury and Reduce Mature Scar Size.

Coronary reperfusion after acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage ischemic heart muscle. However, subsequent inflammatory responses within the infarct lead to further loss of viable myocardium. Transforming growth factor (TGF)-β1 is a potent anti-inflammatory cytokine released in response to tissue injury.

Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction.

Myocardial infarction is a leading cause of morbidity and mortality. While reperfusion is now standard therapy, pathological remodelling leading to heart failure remains a clinical problem. Cellular senescence has been shown to contribute to disease pathophysiology and treatment with the senolytic navitoclax attenuates inflammation, reduces adverse myocardial remodelling and results in improved functional recovery.

Heart Disease and Ageing: The Roles of Senescence, Mitochondria, and Telomerase in Cardiovascular Disease.

During ageing molecular damage leads to the accumulation of several hallmarks of ageing including mitochondrial dysfunction, cellular senescence, genetic instability and chronic inflammation, which contribute to the development and progression of ageing-associated diseases including cardiovascular disease. Consequently, understanding how these hallmarks of biological ageing interact with the cardiovascular system and each other is fundamental to the pursuit of improving cardiovascular health globally. This review provides an overview of our current understanding of how candidate hallmarks contribute to cardiovascular diseases such as atherosclerosis, coronary artery disease and subsequent myocardial infarction, and age-related heart failure.

Anthracycline-induced cardiotoxicity and senescence.

Cancer continues to place a heavy burden on healthcare systems around the world. Although cancer survivorship continues to improve, cardiotoxicity leading to cardiomyopathy and heart failure as a consequence of cancer therapy is rising, and yesterday's cancer survivors are fast becoming today's heart failure patients. Although the mechanisms driving cardiotoxicity are complex, cellular senescence is gaining attention as a major contributor to chemotherapy-induced cardiotoxicity and, therefore, may also represent a novel therapeutic target to prevent this disease.

MiR-126-3p Is Dynamically Regulated in Endothelial-to-Mesenchymal Transition during Fibrosis.

In fibrotic diseases, myofibroblasts derive from a range of cell types including endothelial-to-mesenchymal transition (EndMT). Increasing evidence suggests that miRNAs are key regulators in biological processes but their profile is relatively understudied in EndMT. In human umbilical vein endothelial cells (HUVEC), EndMT was induced by treatment with TGFβ2 and IL1β.

Rapid fall in circulating non-classical monocytes in ST elevation myocardial infarction patients correlates with cardiac injury.

Myocardial infarction leads to a rapid innate immune response that is ultimately required for repair of damaged heart tissue. We therefore examined circulating monocyte dynamics immediately after reperfusion of the culprit coronary vessel in STEMI patients to determine whether this correlated with level of cardiac injury. A mouse model of cardiac ischemia/reperfusion injury was subsequently used to establish the degree of monocyte margination to the coronary vasculature that could potentially contribute to the drop in circulating monocytes.

Arterial endoglin does not protect against arteriovenous malformations.

Introduction: Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling. Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder hereditary haemorrhagic telangiectasia (HHT), characterised by arteriovenous malformations (AVMs). However, the vessel-specific role of ENG and ALK1 proteins in protecting against AVMs is unclear.

Loss of Endothelial Endoglin Promotes High-Output Heart Failure Through Peripheral Arteriovenous Shunting Driven by VEGF Signaling.

Rationale: ENG (endoglin) is a coreceptor for BMP (bone morphogenetic protein) 9/10 and is strongly expressed in endothelial cells. Mutations in lead to the inherited vascular disorder hereditary hemorrhagic telangiectasia characterized by local telangiectases and larger arteriovenous malformations (AVMs); but how ENG functions to regulate the adult vasculature is not understood.

Objective: The goal of the work was to determine how ENG maintains vessel caliber in adult life to prevent AVM formation and thereby protect heart function.

Role of soluble endoglin in BMP9 signaling.

Endoglin (ENG) is a coreceptor of the transforming growth factor-β (TGFβ) family signaling complex, which is highly expressed on endothelial cells and plays a key role in angiogenesis. Its extracellular domain can be cleaved and released into the circulation as soluble ENG (sENG). High circulating levels of sENG contribute to the pathogenesis of preeclampsia (PE).

Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis.

Clinical trials of stem cell therapy to treat ischemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis, and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue.

Using MRI to predict future adverse cardiac remodelling in a male mouse model of myocardial infarction.

Background: Mice are frequently used in research to examine outcomes of myocardial infarction (MI) and to investigate therapeutic interventions at an early pre-clinical stage. The MI model is generated by surgically occluding a major coronary artery, but natural variation in murine coronary anatomy can generate variable outcomes that will inevitably affect the accuracy of such investigations. The aim of this study was to use MRI to derive the most sensitive early variable that could be used to predict subsequent adverse cardiac remodelling in a male mouse model of MI.

Endothelial depletion of Acvrl1 in mice leads to arteriovenous malformations associated with reduced endoglin expression.

Rare inherited cardiovascular diseases are frequently caused by mutations in genes that are essential for the formation and/or function of the cardiovasculature. Hereditary Haemorrhagic Telangiectasia is a familial disease of this type. The majority of patients carry mutations in either Endoglin (ENG) or ACVRL1 (also known as ALK1) genes, and the disease is characterized by arteriovenous malformations and persistent haemorrhage.