Editorial [Hot Topic: Experimental Models for the Study of Drugs Used to Prevent and Treat Vascular Diseases (Executive Editors: C.S. Thompson, D.P. Mikhailidis and K.I. Paraskevas)]

Vascular disease is a major cause of morbidity and mortality worldwide. Reducing the incidence of deaths due to vascular causes holds implications for national economies worldwide [1]. On this basis, several animal models have been developed to replicate human vascular diseases in order to study their pathophysiology. This issue of the Current Pharmaceutical Design discusses some of these models. In this Editorial we will briefly review each article in this Special Issue and we will also briefly consider a few additional models. Thompson describes various animal models of diabetes and also highlights those most commonly used to evaluate diabetic micro- and macrovascular complications [2]. Paraskevas et al. describe the animal models developed for the study of abdominal aortic aneurysms (AAAs) [3]. This review focuses on the pathomechanisms involved in the development of AAAs and the different treatment modalities for their management. Kolovou et al. describe apolipoprotein E (Apo E) knock out mouse models, which were developed to study atherosclerosis and cardiovascular diseases [4]. The applications of these models in the study of lipoprotein metabolism, arterial wall stiffness and the effect of various diets/ drugs are also discussed. Tatlisumak et al. describe the various animal models for the study of the pathophysiology and management of stroke. In one review, they discuss rodent models of hemorrhagic stroke [5]. In the second review, they discuss models of ischemic stroke [6]. They provide a detailed analysis of why these animal models are important for our understanding of the pathophysiology of stroke and brain ischemia and how they can be used to discover (and test) novel treatment strategies. The advantages and disadvantages of each reported model are also outlined. Shiba et al. describe models of angiogenesis [7]. They discuss the mechanism of neovascularization and the applications of therapeutic angiogenesis in humans based on animal models. Xirouchakis et al. describe experimental models of non-alcoholic fatty liver [8]. This condition is associated with both metabolic syndrome and diabetes. Inevitably therefore, there is a link between fatty liver and an increased risk of vascular disease. In addition, several other models have been developed for the study of vascular disease. This Editorial briefly addresses some of them. Peripheral Arterial Disease (PAD) Several animal models for the study of PAD have been described. Lower limb ischemia affects a large percentage of the population. One of the most rapidly growing treatment modalities for the management of PAD is therapeutic angiogenesis [9]. Animal models of hindlimb ischemia were developed to evaluate the beneficial effects of autologous bone marrow cell infusion [10,11], vascular endothelial growth factor (VEGF) [12] and platelet-derived endothelial cell growth factor (PD-ECGF) [13] for the induction of angiogenesis. Other models were developed for the establishment of diagnostic tests for the evaluation and quantification of angiogenesis [14-17]. These models provide insight in the pathophysiology and management of PAD. Application of these preliminary results in humans holds implications for a different therapeutic approach. Hyperhomocysteinemia Hyperhomocysteinemia has been proposed as an independent risk factor for atherothrombotic disease [18-20]. Supplementation with methionine, homocysteine and/or depletion of folic acid and B vitamins can induce mild to severe hyperhomocysteinemia [21,22]. Mice with a heterozygous cystathione β-synthase-deficiency (enzymes responsible for homocysteine metabolism) develop endothelial dysfunction by decreasing vascular nitric oxide bioavailability, thereby leading to impaired vasorelaxation [23,24]. Animal models of hyperhomocysteinemia have extended many of the proposed mechanisms linking this abnormality with atherogenesis. However, the findings reported in animal models are not necessarily reproduced in human studies [25]. Hypertension Hypertension is an important risk factor for cardiovascular and cerebrovascular disease. Research on pathophysiology and treatment of hypertensive brain damage may benefit from the availability of animal models [26-30]. Spontaneously hypertensive rats represent the most commonly used animal model. In these rats, cerebrovascular changes, brain atrophy, loss of nerve cells in cerebrocortical areas and glial reaction occur. The influence of anti-hypertensive treatment on brain structure and function in animal models of hypertension has also been investigated [26-30]..........