Reversal of hypoxia in murine atherosclerosis prevents necrotic core expansion by enhancing efferocytosis.

Objective: Advanced murine and human plaques are hypoxic, but it remains unclear whether plaque hypoxia is causally related to atherogenesis. Here, we test the hypothesis that reversal of hypoxia in atherosclerotic plaques by breathing hyperoxic carbogen gas will prevent atherosclerosis.

Approach And Results: Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) were fed a Western-type diet, exposed to carbogen (95% O2, 5% CO2) or air, and the effect on plaque hypoxia, size, and phenotype was studied.

[Lp-PLA2 and sPLA2: cardiovascular biomarkers].

Phospholipases A2 (PLA2) belong to a superfamily of enzymes that catalyze the hydrolysis of glycerophospholipids at the sn-2 position, producing nonesterified fatty acids and lysophospholipids. Many experimental studies have shown that PLA2 are involved in lipid metabolism and immuno-inflammatory response and participate in the development of atherosclerosis. In humans, therapeutic approaches based on the inhibition of PLA2 are currently in development.

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.

Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance.