Evaluating micro- and macro-vascular disease, the end stage of atherosclerosis, in rat models

Development of effective treatment or, more critically, preventative measures against atherosclerosis and cardiovascular disease will require animal models that mimic the disease processes seen in humans and permit identification of the genetic and physiological factors. The Rat is normally resistant to cardiovascular disease, but a number of genetic mutations make affected strains of rats highly susceptible to atherosclerosis and micro- and macro-vascular disease that is highly analogous to human disease. These models of obesity develop the metabolic syndrome and type 2 diabetes, hyperinsulinemia, hyperlipidemia, vascular and myocardial dysfunction, and end-stage lesions in the heart and kidney. The models offer the prospect of both genetic and molecular biology studies that are linked directly to spontaneous cardiovascular disease and exploration of putative preventative or treatment approaches, including pharmaceutical agents. Use of small animal models of cardiovascular disease is dependent on appropriate experimental design and techniques that take account of the complex nature of the disease processes. Detailed experimental procedures for the use of rat models, including handling and treatment of animals, choice of experimental variables and endpoints, assay methods, and histological and electron microscopy techniques are covered in this chapter.