Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model

Arterial inflammatory responses are thought to be a significant component o f atherosclerotic disease. We describe here, using a transgenic approach, t he mutual perpetuation of immune-mediated arterial inflammation and cholest erol-induced atherosclerosis. Mice expressing the bacterial transgene beta -galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprot ein E-deficient SM-LacZ mice (SM-LacZ/apoE(-/-)) developed myocarditis and arteritis after immunization with dendritic cells presenting a beta -galact osidase-derived immunogenic peptide. Hypercholesterolemia amplified acute a rteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE(-/-) mice, but had no major impact on acute myocarditis or the subsequent devel opment of dilated cardiomyopathy. Conversely, arteritis significantly accel erated cholesterol-induced atherosclerosis. Taken together, these data demo nstrate that the linkage of immune-mediated arteritis and hypercholesterole mia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis.