Spontaneous Atherosclerosis in Pigeons: A Good Model of Human Disease

Abstract

Avian models of human atherosclerosis such as the chicken, turkey, quail, and pigeon are not currently in widespread use, but have a longer and richer history than most mammalian models of cardiovascular disease. In 1874, the first angioplasty surgery of the aortic wall was performed in birds (Roberts & Strauss, 1965). Spontaneous (non-induced) atherosclerosis in the chicken was first described in 1914 (Roberts & Strauss, 1965), and it has been repeatedly observed that avian lesions bear close resemblance to their human counterparts (Clarkson et al., 1959; Herndon et al., 1962; Cornhill et al., 1980b; Qin & Nishimura, 1998). The pigeon (Columba livia) is especially suited for genetic studies of atherosclerosis because susceptible and resistant strains exist in the natural population (Herndon et al., 1962; St. Clair, 1983) eliminating the need to construct an artificial phenotype through genetic or dietary manipulation. In fact, it has been suggested that the White Carneau (WC) pigeon may be one of the most appropriate models of early human lesions (Cornhill et al., 1980b; St. Clair, 1998; Moghadasian et al., 2001). This review is comprised of background information on human atherosclerosis, a description of other animal models and details of the pigeon model. Atherosclerosis is the most common form of heart disease, a general term encompassing a variety of pathologies affecting the heart and circulatory system. More specifically, atherosclerosis is a disease of the blood vessel itself, and is most likely to develop at branch points and other regions of low shear stress along the arterial tree, such as the celiac bifurcation of the aorta, and in coronary and carotid arteries (Bassiouny et al., 1994; Kjaernes et al., 1981). The disease is a chronic and multifactorial result of both environmental and genetic factors, as well as their interactions (Breslow, 2000; Moghadasian et al., 2001). It remains the number one cause of morbidity and mortality in the United States and other developed countries (Gurr, 1992; Wagner, 1978). Arterial lesions begin to develop during childhood as lipid-filled foam cells making up “fatty streaks” (Napoli et al., 2002; Stary, 1989), and slowly progress into complex plaques consisting of multiple cell types, intraand extracellular cholesterol esters, calcium deposits, proteoglycans, and extensive connective tissue. The final and terminating atherosclerotic event is blood vessel occlusion, often caused by plaque rupture, which can lead to a heart attack, stroke, or embolism, depending on the location of the affected artery. However, not all fatty streaks progress to advanced lesions (Getz, 2000), and their progression/regression rate, although well correlated with classical risk factors, is unique to each individual.