Basic Mechanisms in Atherosclerosis: The Role of Calcium.

In the beginning, atherosclerosis was considered to be the result of passive lipid accumulation in the vascular walls. After tremendous technological advancements in research, we are now able to almost admire the complexity of the atherosclerotic process. Atherosclerosis is a chronicinflammatory condition that begins with the formation of calcified plaque, influenced by a number of different factors inside the vascular wall in large and mid-sized arteries. Calcium mineralization of the lumen in the atherosclerotic artery promotes and solidifies plaque formation causing narrowing of the vessel. Soft tissue calcification associated with tissue denegation or necrosis is a passive precipitation event. The process of atherogenesis is mainly driven by CD4+ T cells, CD40L, macrophages, foam cells with elevated transcription of many matrix metalloproteinases, osteoblasts, cytokines, selectins, myeloperoxidases, vascular adhesion molecules (VCAM), and smooth muscle cells. Our knowledge in the genesis of atherosclerosis has changed dramatically in the last few years. New imaging techniques such as intravascular ultrasound or IVUS have made possible to investigate atherosclerosis in early stages. Arterial calcification emerges from two different types, the medial-elastin dependent and the intimal, both of which are directly related to atherosclerosis due to osteoblast differentiation of vascular smooth muscle cells. The deposition of minerals in the form of calcium (Ca(2+)) initially emerges from the inorganing mineral octacalcium phosphate [Ca8H2(PO4)6.5H2O] to the form of Hydroxylapatite [Ca10(PO4)6(OH)2]. This review is devoted to broaden the understanding regarding atherosclerosis and the central role of calcium in the development of the condition.

Duration of Dual Antiplatelet Therapy After Coronary Stenting.

BACKGROUND: Dual antiplatelet therapy (DAPT) is one of the cornerstones of coronary artery disease (CAD) treatment. Standard DAPT requires one of, P2Y12 receptor inhibitors, clopidogrel, prasugrel or ticagrelor as an adjunct therapy to aspirin administration. The decision over DAPT duration depends on the evaluation of thrombotic risk and the assessment of the probability for major bleeding events. METHODS: The goal of this work was to identify which would be the appropriate combination of antiplatelet agents and the optimal duration of DAPT, based on the patient's medical history and clinical characteristics. A thorough search of PubMed and the Cochrane Database was conducted in order to identify randomized controlled trials, observational studies, current ESC and ACC/AHA guidelines and novel articles on the subject. RESULTS: The decision over DAPT duration is based on a careful approach which requires the evaluation of thrombotic risk and the assessment of the probability for major bleeding events. A series of aspects and special conditions may influence the duration of DAPT after stenting e.g. the type of the implanted stent (DES or BMS) or if the commencement of DAPT is administered in the context of an acute coronary syndrome or in the setting of stable CAD. Current guidelines can assist clinicians in making decisions but treating patients in special groups e.g. with diabetes mellitus or the elderly people can be very demanding. CONCLUSION: Studies which examined optimal DAPT duration, displayed controversial results, mainly observed because of the discrepancy and heterogeneity between different study designs or the decision of a great proportion of investigators to statistically test for non-inferiority. A careful, patient-centered approach, which considers thrombotic risk versus the risk for bleeding complications and other individual characteristics and comorbidities, is required when deciding DAPT duration.

The Role of Endothelial Dysfunction in Aortic Aneurysms.

Abdominal aortic aneurysm is a vascular disease which, despite the fact that it shares common risk factors with atherosclerosis, develops in parallel but as a partly independent process, through different pathogenic mechanisms. The pathogenic mechanisms involve metalloproteinase and collagenase activation, median and adventitial degradation, elastin lysis, vascular smooth cells transformation and apoptosis, collagen production and lysis imbalance combined with excessive inflammatory infiltration. Endothelial cells respond to a number of stimulating factors, including smoking, hypertension and AT1 receptor stimulation and non-uniform distribution of wall stress. Their ability to produce NO is crucial in order to adapt. Endothelial cells contribute to AAA development due to increased oxidative stress which is partly mediated by impaired NO bioavailability due to endothelial dysfunction and NADPH oxidase overexpression. In addition, they express several molecules among which adherence molecules, selectins, endothelin-1, regulating inflammatory infiltration and oxidative stress. Inflammatory cells consist of monocytes, polymorphonuclear neutrophils and lymphocytes and they are involved in the degrading process in the aortic wall by secreting proteolytic enzymes or by releasing interleukins which mediate the inflammation response. Endothelial dysfunction and arterial stiffness reflect on indices like FMD, carotid-femoral PWV and augmentation index, sometimes with controversial results. At present, surgical treatment is the only option provided in patients with large AAA, in particular. Focusing on the emerging role of endothelial cells in AAA pathology may contribute in creating new therapeutic options in a disease which has not yet a well-accepted, implemented pharmaceutical treatment.

Novel Inflammatory Biomarkers in Cardiovascular Therapeutics.

Inflammation has been established as an important determinant of cardiovascular disease progression. Currently, clinical examination, laboratory and imaging tests are invaluable for the diagnosis, prognosis and disease monitoring. Novel inflammatory biomarkers are also used to better restratify patients in risk groups but their potential to guide treatment decisions and management of patients has not been extensively evaluated. Therefore, in this review article we present the most recent data concerning the use of inflammatory biomarkers in cardiovascular therapeutics.