The commonest cause of death in both humans and captive chimpanzees is “heart disease,” manifested either as sudden “heart attacks” or as progressive heart failure (Lammey et al., 2008; Varki et al., 2009). However, early case reports suggested that the diseases in humans and chimpanzees are different, and recent studies have confirmed this notion (Lammey et al., 2008; Varki et al., 2009). Chimpanzees and other NHHs develop a progressive fibrotic replacement of the heart muscle (interstitial myocardial fibrosis), which can cause sudden death by altering heart rhythm or slower death by progressive cardiac failure. “Heart disease” in humans is different, caused by deposition of cholesterol in atherosclerotic plaques in the walls of large blood vessels, including coronary arteries (Pham et al., 2009; Varki et al., 2009). This deposition results in sudden or progressive loss of blood supply, explaining the common “heart attack” of humans (“myocardial infarction”) or progressive heart failure caused by “ischemic heart disease.” Although captive chimpanzees and others NHHs do have atherosclerosis (Varki et al., 2009), myocardial infarction and ischemic heart disease are rare, despite risk factors such as hypertension (Denton et al., 1995) and high levels of LDL cholesterol and lipoprotein(a) (Varki et al., 2009). Why do NHHs not often have the kind of heart disease common in humans? Conversely, why do humans not often suffer from the fibrotic heart disease so common in our closest evolutionary cousins?
For unclear reasons, accumulation of dietary Neu5Gc in human tissues is not uniform, and it tends to accumulate particularly in epithelial cells lining hollow organs (where carcinomas develop) or in the endothelium lining blood vessels (where atherosclerosis occurs). In fact, cultured endothelial cells fed with Neu5Gc (with Neu5Ac as a negative control) bind anti-Neu5Gc antibodies and deposit complement from human serum, resulting in cellular activation, expression of adhesion molecules, and binding of monocytes (Pham et al., 2009). Thus, although underlying mechanisms exist for many vascular diseases, we suggest that endothelial incorporation of Neu5Gc combines with circulating anti-Neu5Gc antibodies to aggravate processes such as atherosclerosis (Pham et al., 2009). Indeed, human atherosclerotic lesions show Neu5Gc accumulation not just in overlying endothelium but also inside the plaque (Pham et al., 2009). This Neu5Gc accumulation may facilitate production of anti-Neu5Gc