Cardioprotection by functional and dysfunctional High-density lipoproteins (HDL) in comorbidities: molecular mechanisms and therapeutic exploitation (B11)

在WP1中，我们将测试功能性HDL在心脏I/R损伤中的心脏保护潜力，并确定SR-BI在存在和不存在S1P受体时作为HDL-S1P依赖性和非依赖性心脏保护靶点的作用。在WP2中，我们将比较功能性和功能不全（T2DM、MI和CAD） HDL对心脏的保护作用，并建立心脏保护HDL标准。在WP3中，我们将在T2DM小鼠模型中评估糖尿病HDL对心脏的保护作用，以区分局部难治性和HDL功能障碍。最后，结合几种心脏保护HDL特性的定制HDL颗粒将在实验性和自发性小鼠心肌梗死中进行测试。

In WP1, we will test the cardioprotective potential of functional HDL in cardiac I/R injury and identify the contribution of the SR-BI in the presence and absence of S1P receptors as targets for HDL-S1P-dependent and -independent cardioprotection. In WP2, we will compare cardioprotection by functional and dysfunctional (T2DM, MI and CAD) HDL and establish cardioprotective HDL criteria. In WP3, we will assess cardioprotection by diabetic HDL in a mouse model of T2DM to differentiate local refractoriness from HDL dysfunction. Finally, custom-tailored HDL particles combining several cardioprotective HDL characteristics will be tested in experimental and spontaneous mouse MI.