No abstract

Atrial fibrillation (AF) is associated with structural, electrical, and contractile remodeling of the atria. Development and progression of atrial fibrosis is the hallmark of structural remodeling in AF and is considered the substrate for AF perpetuation. In contrast, experimental and clinical data on the effect of ventricular fibrotic processes in the pathogenesis of AF and its complications are controversial. Ventricular fibrosis seems to contribute to abnormalities in cardiac relaxation and contractility and to the development of heart failure, a common finding in AF. Given that AF and heart failure frequently coexist and that both conditions affect patient prognosis, a better understanding of the mutual effect of fibrosis in AF and heart failure is of particular interest. In this review paper, we provide an overview of the general mechanisms of cardiac fibrosis in AF, differences between fibrotic processes in atria and ventricles, and the clinical and prognostic significance of cardiac fibrosis in AF.

The important role of the vascular endothelium in cardiovascular health is increasingly recognized. However, mature endothelial cells possess limited regenerative capacity. There is therefore much interest in circulating endothelial progenitor cells (EPCs) among the scientific community, especially into their purported role in maintenance of endothelial integrity and function, as well as postnatal neovascularization. It has been suggested that these cells might not only be responsible for the continuous recovery of the endothelium after injury/damage, but also might take part in angiogenesis, giving the hope of new treatment opportunities. Indeed, there is accumulating evidence showing reduced availability and impaired EPC function in the presence of both cardiovascular disease and associated comorbid risk factors. Thus, many studies into the potential for use of EPCs in the clinical setting are being undertaken. The goal of this review article is to provide an overview of data relevant to the clinical role of EPCs and perspectives for treatment of cardiovascular disorders.

Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function.

New vessel formation inside the arterial wall and atherosclerotic plaques plays a critical role in pathogenesis of heart attacks and strokes. The 2 known mechanisms resulting in the formation of new vessels within the plaque are local ischemia and inflammation. Blood monocytes play an important role in both processes. First, they express receptors for vascular endothelial growth factor and some of them may serve as circulating ancestors of endothelial cells. Second, monocytes are associated with inflammation by synthesis of inflammatory molecules following their activation (e.g., after stimulation of Toll-like receptors). Neovascularization is a reparative response to ischemia, and includes 3 processes: angiogenesis, arteriogenesis, and vasculogenesis. Angiogenesis, the formation of new capillary vessels is known to occur in response to a hypoxic environment. The interaction between leukocytes and vascular wall via overexpression of various molecules facilitates the migration of inflammatory cells into the plaque microenvironment. Monocytes are intimately involved in tissue damage and repair and an imbalance of these processes may have detrimental consequences for plaque development and stability. Importantly, monocytes are comprised of distinct subsets with different cell surface markers and functional characteristics and this heterogeneity may be relevant to angiogenic processes in atherosclerosis. The aim of this review article is to present an overview of the available evidence supporting a role for monocytes in angiogenesis and atherosclerosis.