Arterial Injury due to Infections in Early Life-A Possible Link in Coronary Heart Disease (Functional and Structural Studies in Animals and Children)

Although the clinical manifestations of atherosclerotic CHD occur in adult life, the preclinical phase begins long before, seemingly already in childhood. There is supportive evidence from both epidemiological studies and animal experiments that infections could contribute to the pathogenesis of arterial disease, including atherosclerosis. It has been hypothesised that damage to the vascular endothelium might serve as a pathogenic link, and the magnitude of it might determine the type of disease, i.e., acute or chronic. The objectives of the studies were to asses the impact of chronic and acute infections on the arterial structure and function in young experimental animals and children. Arterial relaxation responses and changes in coronary flow velocity in response to endothelium-dependent agonists, such as methacholine and bradykinin, were used as markers of functional changes in two animal models: young apoE-KO mice and piglets. C. pneumoniae and H. pylori were used as infectious stimuli in these models. Ultrasound-detected carotid artery intima-media thickness served as a marker of structural changes in children during their acute infectious illness, and three months after. Our studies showed that chronic infection with C. pneumoniae alters the muscarinic-mediated endothelium-dependent vasodilator function of aortas in apoE-KO mice, whereas acute infection with the same pathogen results in widespread coronary endothelial dysfunction and a pro-coagulant status in piglets. The responses to bradykinin were preserved or even augmented in chronically infected apoEKO mice, suggesting active kinin-induced compensatory mechanisms that could involve NO and prostacyclin. C. pneumoniae and H. pylori appeared to have additive effects in the development of endothelial dysfunction and early atherosclerotic changes. Finally, children with acute systemic infections had pro-atherogenic lipid changes during their acute illness, and were followed by carotid artery thickening, whilst antibiotic treatment was associated with less thickening. The findings support the infectious hypothesis of CHD, and the mechanistic link of endothelial dysfunction. It is tempting to believe that endothelial function interventions initiated early in life particularly in pediatric population with serological evidence of two or more chronic infections might lower the CHD risk in adult life. Likewise more effective preventive and curative measures for combating infections in childhood appear necessary.