Investigation of the impact of endothelial Pnpla2 (Atgl) deletion in mice using snRNAseq. Pnpla2-KO mice snRNAseq

To investigate the impact of endothelial Atgl (Pnpla2) deletion and subsequent endothelial lipid droplet accumulation Atgl-floxed (Atglfl/fl) mice were cross-bred with endothelial cell-specific Cdh5 CreERT2 mice to generate mice with an inducible endothelial cell-specific Atgl-knockout. For analysis, 6-8 week old male mice (Atgl fl/fl LFD, ecAtglKO LFD, Atgl fl/fl HFpEF, ecAtglKO HFpEF, n = 4) were used. To develop HFpEF mice were subjected to a hypertensive-obese two–hit HFpEF model. Briefly, mice received either LFD (10 % energy from fat) or HFD (60 % energy from fat) and N[w]-nitro-l-arginine methyl ester (L-NAME, 0.5 g/L, pH 7.4) in drinking water ad libitum for 15 weeks.

为探究内皮细胞脂肪甘油三酯脂肪酶（Adipose Triglyceride Lipase, Atgl；Pnpla2）敲除及其后续引发的内皮细胞脂滴蓄积的影响，本研究将Atgl条件性基因敲除（Atgl-floxed, Atglfl/fl）小鼠与内皮细胞特异性Cdh5-CreERT2工具鼠杂交繁育，以构建诱导型内皮细胞特异性Atgl基因敲除小鼠。实验分析选用6~8周龄雄性小鼠，分为Atgl fl/fl LFD组、ecAtglKO LFD组、Atgl fl/fl HFpEF组、ecAtglKO HFpEF组，每组n=4。为构建射血分数保留型心力衰竭（Heart Failure with Preserved Ejection Fraction, HFpEF）小鼠模型，本研究采用高血压-肥胖双打击HFpEF造模方案：简言之，小鼠分别饲喂脂肪供能占比10%的低脂饲料（Low Fat Diet, LFD）或脂肪供能占比60%的高脂饲料（High Fat Diet, HFD），同时自由饮用添加了0.5 g/L、pH 7.4的Nω-硝基-L-精氨酸甲酯（L-NAME）的饮用水，持续干预15周。