Expression of Myeloperoxidase in Patient-Derived Endothelial Colony-Forming Cells-Associations with Coronary Artery Disease and Mitochondrial Function.

Background And Aims: Myeloperoxidase (MPO) plays a critical role in the innate immune response and has been suggested to be a surrogate marker of oxidative stress and inflammation, with elevated levels implicated in cardiovascular diseases, such as atherosclerosis and heart failure, as well as in conditions like rheumatoid arthritis and cancer. While MPO is well-known in leukocytes, its expression and function in human endothelial cells remain unclear. This study investigates MPO expression in patient-derived endothelial colony-forming cells (ECFCs) and its potential association with CAD and mitochondrial function.

Serum Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 (sLOX-1) Is Associated with Atherosclerosis Severity in Coronary Artery Disease.

Risk-factor-based scoring systems for atherosclerotic coronary artery disease (CAD) remain concerningly inaccurate at the level of the individual and would benefit from the addition of biomarkers that correlate with atherosclerosis burden directly. We hypothesized that serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) would be independently associated with CAD and investigated this in the BioHEART study using 968 participants with CT coronary angiograms, which were scored for disease burden in the form of coronary artery calcium scores (CACS), Gensini scores, and a semi-quantitative soft-plaque score (SPS). Serum sLOX-1 was assessed by ELISA and was incorporated into regression models for disease severity and incidence.

Novel Strategies in the Early Detection and Treatment of Endothelial Cell-Specific Mitochondrial Dysfunction in Coronary Artery Disease.

Although elevated cholesterol and other recognised cardiovascular risk factors are important in the development of coronary artery disease (CAD) and heart attack, the susceptibility of humans to this fatal process is distinct from other animals. Mitochondrial dysfunction of cells in the arterial wall, particularly the endothelium, has been strongly implicated in the pathogenesis of CAD. In this manuscript, we review the established evidence and mechanisms in detail and explore the potential opportunities arising from analysing mitochondrial function in patient-derived cells such as endothelial colony-forming cells easily cultured from venous blood.

Development and clinical translation of P2X7 receptor antagonists: A potential therapeutic target in coronary artery disease?

The purinoceptor 7 receptor (P2XR) plays an important role in promoting inflammation in response to accumulating damage-associated molecular patterns (DAMPs) released from stressed or apoptotic cells and has been connected to various pathological conditions. The initial investment by large pharmaceutical companies such as AstraZeneca and Pfizer led to the development of several classes of P2XR antagonists for the treatment of rheumatoid arthritis and Crohn's disease. While these compounds showed early promise as therapeutic agents and were found to potently inhibit adenosine triphosphate (ATP)-induced release of interleukin 1 beta (IL-1β) in patient-derived monocytes primed with lipopolysaccharide (LPS), they failed to elicit a therapeutic benefit in phase II clinical trials.

Patient Endothelial Colony-Forming Cells to Model Coronary Artery Disease Susceptibility and Unravel the Role of Dysregulated Mitochondrial Redox Signalling.

Mechanisms involved in the individual susceptibility to atherosclerotic coronary artery disease (CAD) beyond traditional risk factors are poorly understood. Here, we describe the utility of cultured patient-derived endothelial colony-forming cells (ECFCs) in examining novel mechanisms of CAD susceptibility, particularly the role of dysregulated redox signalling. ECFCs were selectively cultured from peripheral blood mononuclear cells from 828 patients from the BioHEART-CT cohort, each with corresponding demographic, clinical and CT coronary angiographic imaging data.

The novel P2X7 receptor antagonist PKT100 improves cardiac function and survival in pulmonary hypertension by direct targeting of the right ventricle.

In pulmonary hypertension (PH) a proinflammatory milieu drives pulmonary vascular remodeling, maladaptive right ventricular (RV) remodeling, and right-sided heart failure. There is an unmet need for RV-targeted pharmaco-therapies to improve mortality. Targeting of the P2X7 receptor (P2X7R) reduces pulmonary pressures; however, its effects on the RV are presently unknown.