Radial artery intima-media thickening is a sensitive marker of atherosclerosis and coronary artery stenosis, a lesson from a 6-year study of a spontaneous monkey model.

Abstract

Atherosclerosis is the primary driver of cardiovascular and cerebral vascular diseases globally. Atherosclerotic plaques have been detected in multiple arterial locations, such as the aorta, carotids, and coronaries. However, it remains uncertain if there are variations in susceptibility and association among arteries of different calibers. Utilizing a spontaneous rhesus monkey model of metabolic syndrome (MetS), we assessed the susceptibility of atherosclerosis among the radial artery, femoral artery, and carotid artery and their correlation with coronary heart disease (CHD). The development of atherosclerosis in the three arteries mentioned above was evaluated by Intima-media thickness (IMT) and plaques using echo imaging over 6 years in a cohort of elderly monkeys with metabolic disorders. Coronary artery stenosis was assessed by coronary flow reserve (CFR) simultaneously. The diagnosis was further confirmed by histopathological examination, and RNA sequencing was employed to probe the transcriptional underpinnings of atherosclerotic development. The spontaneous development of atherosclerosis was observed in elderly monkeys, and the incidence of atherosclerosis was increased by three times in the MetS monkeys compared to the age-matched control group. During the 6-year follow-up, there was a notable increase in the IMT across all three arteries, with the radial artery showing the most pronounced thickening. Moreover, only the radial IMT correlated with CFR, suggesting its potential as a non-invasive diagnostic indicator for CHD. Histopathology confirmed the findings by echo imaging and identified different extracellular matrix (ECM) remodeling patterns in the arteries. In addition, transcriptomic analysis revealed that ECM remodeling and inflammation-related pathways were significantly upregulated in radial atherosclerotic samples, multiple inflammatory pathways were upregulated in the femoral lesion samples, and the carotid samples failed to enrich any pathways due to a lack of differentially expressed genes compared to the control samples. Non-human primates, which share extensive genetic and physiological similarities with humans, develop atherosclerosis spontaneously. This provides an invaluable platform for investigating the intricate mechanisms of arterial disease and evaluating potential treatments. Using the monkey model, we identified the radial artery as a sensitive indicator for assessing the occurrence and progression of atherosclerosis and coronary stenosis.