Editorial [ Special Issue on Atherosclerosis Executive Editors: Pedro R. Moreno, Javier Sanz and Valentin Fuster ]

Atherothrombosis continues to be the most important cause of death and disability in western countries, and for 2020 will also be the main cause in developing countries. Recent paramount research performed within the last few years highlight the importance of new pathophysiological, clinical, and therapeutic approaches to atherothrombosis, creating new pathways for diagnosis, treatment and prevention. This supplement organized in three sections is devoted to novel concepts covering the disease, from early atherogenesis to plaque rupture and thrombosis. The first section entitled "Basic and Experimental" is composed by six articles addressing the latest understanding of the cellular and molecular mechanisms of the disease. In the first review, entitled "Cell biology and lipoproteins in atherosclerosis", Dr. Badimon et al., review the complex interaction among inflammatory cells, vascular elements, and lipoproteins leading to early atherogenesis. Specific attention is paid to the role of the endothelial cell as the central player for cell adhesion, subendothelial retention and modification of LDL, intracellular lipid accumulation, and extracellular matrix formation in the vascular wall. In the second review entitled "Neovascularization in human atherosclerosis", Dr. Moreno et al., review the role of vasa vasorum in health and disease, covering the cellular and molecular aspects of atherothrombosis neovascularization. The role of neovessels from early atherogenesis to plaque rupture and thrombosis is covered. Furthermore, the role of neovessels in restenosis and plaque regression is also addressed, providing the reader extensive knowledge in this evolving and promising field. In the third article entitled "Intraplaque Hemorrhage" Dr. Levy et al., review the pathophysiological consequences of red blood cell extravasation within atherosclerotic lesions, focusing on the potent oxidative and pro-inflammatory effects of Hemoglobin, leading to macrophage activation and plaque destabilization. The main defense mechanism against hemoglobin, the protein Haptoglobin is also reviewed, with special attention to the diabetic population. In the fourth article entitled "Link between inflammation and thrombogenicity in atherosclerosis" Dr. Viles et al., review the concept of vulnerable plaque, vulnerable blood, and vulnerable patient. Of note, the role of tissue factor, platelets, apoptosis, and other pro-thrombotic mediators is elegantly addressed, summarizing the interactions between inflammation and coagulation within the setting of atherothrombotic disease. In the fourth article of this section entitled "Metabolic syndrome, diabetes, and peroxisomal proliferator activated receptors" Dr. Meerarani., et al review the complex interaction between insulin resistance, endothelial dysfunction, and pro-inflammatory gene regulation leading to an increased atherothrombotic state. The pivotal role of HDL and the emerging role of peroxisomal proliferator activator receptors in disease stabilization are also addressed, providing the reader with a comprehensive approach to atherothrombosis in patients with metabolic syndrome. Finally, in the last article of this section entitled "Molecular determinants of vascular calcification: a bench to bedside review" Dr. Dellegrottaglie et al., review the mechanisms triggering osteogenesis of the vessel wall associated with the loss of inhibitory factors responsible for enhanced bone turnover. Of note, the interactions between the receptor activator nuclear factor kB, the multiple pro-inflammatory cytokines and the non-collagenous proteins including osteopontin and osteoprotegrin, are reviewed. The second section entitled "Clinical imaging and biomarkers of atherosclerosis" is composed by four articles addressing the state-of-the-art imaging approach for non-invasive diagnosis and risk-stratification of patients with increased likelihood of developing the disease. In the first article entitled "Calcium scoring and contrastenhanced CT angiography" Dr. Sanz et al., review the clinical application of detecting coronary calcium, and the recent advances in non-invasive, CT coronary angiography. In the second article entitled "Plaque imaging and characterization using magnetic resonance imaging: toward molecular assessment" Sirol et al., review the use of high-resolution magnetic resonance for plaque detection and characterization and the potentials of "molecular Imaging". A variety of molecules present in atherosclerotic plaques serving as targets for specific contrast agents allow for the identification of high-risk atherosclerotic lesions. In the third article entitled "atherosclerosis neovascularization and imaging" Dr. Purushothaman et al., specifically review the role of multiple techniques to visualize neovessels in the vessel wall, with special emphasis in molecular imaging.........