Moderate statin treatment reduces prebeta-1 high-density lipoprotein levels in dyslipidemic patients.

BACKGROUND: Elevated plasma levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from macrophages, are associated with increased risk of atherosclerotic coronary heart disease and myocardial infarction. OBJECTIVE: The objective of the study was to assess the effects on prebeta-1 HDL levels of 6-week moderate-dose statin treatment. METHODS: We studied 101 patients (mean age 52.7 years; 53.5% female; 63 with primary hypercholesterolemia; 38 with combined hyperlipidemia) before and after treatment with statins. Mean atorvastatin potency equivalence was 23.6 mg/d. Prebeta-1 HDL plasma levels were measured by immunofixation of agarose gels using anti-apolipoprotein A-1 antibody. RESULTS: We observed a 42.0% reduction of low-density lipoprotein cholesterol (181 ± 56 vs 105 mg/dL, P < .001). Triglyceride (TG) levels decreased by 22.3% (157 vs 122 mg/dL, P < .001), HDL cholesterol levels remained similar (56.0 vs 57.1, P = NS). Levels of prebeta-1 HDL were significantly reduced by 17.9% after statin treatment (mean 11.4 vs 9.4 mg apoA-1/dL, P < .001). The magnitude of this decrease was similar with each of 3 statins (atorvastatin, simvastatin, and rosuvastatin). The decrease in prebeta-1 HDL was strongly associated with the decline in TG, but not with the decline in low-density lipoprotein cholesterol. CONCLUSIONS: The association of high prebeta-1 HDL with coronary heart disease identifies it as an inferential measure of the rate of cholesterol efflux from the artery wall. Our observations demonstrate a reduction of prebeta-1 HDL with statin therapy, partially reflecting the reduced TGs, and probably reflecting a direct beneficial impact on cholesterol efflux.

Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons.

L-type voltage gated calcium channels have an important role in neuronal development by promoting dendritic growth and arborization. A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs). We report that channels with the Timothy syndrome alteration cause activity-dependent dendrite retraction in rat and mouse neurons and in induced pluripotent stem cell (iPSC)-derived neurons from individuals with Timothy syndrome. Dendrite retraction was independent of calcium permeation through the mutant channel, was associated with ectopic activation of RhoA and was inhibited by overexpression of the channel-associated GTPase Gem. These results suggest that Ca(V)1.2 can activate RhoA signaling independently of Ca(2+) and provide insights into the cellular basis of Timothy syndrome and other ASDs.