Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Marathon running leads to transient systolic and more persistent diastolic dysfunction of both the LV and the RV.

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar͞vesicular and stacked discoidal particles reminiscent of those in lecithin͞cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5-6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between Ϸ3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease.atherosclerosis ͉ heart failure ͉ myocardial infarction ͉ unesterified cholesterol C oronary artery atherosclerosis is a major cause of myocardial infarction (MI) and death. We have described a murine model of human coronary heart disease (CHD) (1) that is based on targeted homozygous null mutations in two genes whose products play important roles in normal lipoprotein metabolism and protect mice from atherosclerosis: the high-density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B, type I) (2, 3) and the lipoprotein component apolipoprotein E (apoE) (4-7).Low-fat chow-fed, homozygous null, apoE knockout (KO) mice are hypercholesterolemic (4, 5), develop atherosclerosis between 3 and 4 months of age, and usually live a long life (Ͼ1 year), although older animals can sometimes develop coronary artery occlusions and apparently associated pathology (8, 9). SR-BI controls HDL structure and metabolism and appears to be important for ''reverse cholesterol transport,'' HDL-mediated transport of cholesterol from peripheral tissues (including atherosclerotic plaques) to the liver and then to the bile for excretion (2, 3, 10-16). SR-BI delivers cholesteryl esters and other lipids from HDL to cells via selective lipid uptake (2, 3, 10, 17, 18) and can also mediate un...