Project B11 (Levkau/Polzin)
Cardioprotection by functional and dysfunctional High-density lipoproteins (HDL) in comorbidities: molecular mechansims and therapeutic exploitation
To identify cardioprotection by HDL, we will assess functional HDL in I/R injury and identify the contribution of the HDL receptor scavenger receptor type I (Srb1) by investigating cytoprotective and anti-inflammatory HDL effects. Furthermore, we will compare cardioprotection by functional healthy HDL with that of HDL from patients with AMI, CAD, T2DM and CKD and will define cardioprotective criteria intact in functional and disturbed in dysfunctional HDL. Additionally, we will assess cardioprotection by functional and diabetic HDL in a mouse model of T2DM to differentiate between local tissue refractoriness and HDL dysfunction in cardioprotection. Finally, custom-tailored reconstituted HDL particles and S1P chaperones combining several cardioprotective HDL characteristics will be synthesized and tested in I/R injury.