Kumiko Hirata

Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. To study whether nontransferable lipoprotein lipase has physiological actions, we placed an alpha-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered lipoprotein lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.

BACKGROUND: Normal values for echocardiographic measurements and the relationship between these parameters and age in a large Japanese population are still unknown. METHODS AND RESULTS: A total of 700 healthy Japanese aged 20-79 years underwent 2-dimensional and Doppler echocardiography at collaborating institutions. The respective mean values obtained in men and women were as follows: septal wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; posterior wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; left ventricular (LV) diastolic diameter, 4.8+/-0.4 and 4.4+/-0.3 cm; LV systolic diameter, 3.0+/-0.4 and 2.8+/-0.3 cm; LV diastolic volume, 93+/-20 and 74+/-17 ml; LV systolic volume, 33+/-20 and 25+/-7 ml; LV ejection fraction, 64+/-5 and 66+/-5%; maximum left atrial (LA) volume, 42+/-14 and 38+/-12 ml. Aortic root diameter, LV wall thickness, and LV mass slightly increased with age, whereas indexed LA volume did not vary with age. Diastolic parameters assessed by mitral inflow and mitral annular velocities declined with age, as previously reported. CONCLUSIONS: Normal values of echocardiographic measurements in a large Japanese population are reported for the first time; several systolic and diastolic parameters varied with age. These results provide important reference values that should be useful in routine clinical practice as well as in clinical trials.