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Inflammation impairs eNOS activation by HDL in patients with acute coronary syndrome
Monica Gomaraschi1, Alice Ossoli, Elda Favari
1Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
Insights
High-density lipoprotein (HDL) in ST-elevation myocardial infarction (STEMI) patients with significant inflammation shows impaired ability to activate endothelial nitric oxide synthase (eNOS). HDL structure is compromised in these patients, impacting nitric oxide production.
Area of Science:
- Cardiovascular Science
- Inflammation Biology
- Lipid Metabolism
Background:
- High-density lipoprotein (HDL) plays a crucial role in cardiovascular health.
- Endothelial nitric oxide synthase (eNOS) activation is vital for vascular function.
- The acute-phase inflammatory response (APR) in ST-elevation myocardial infarction (STEMI) can impact HDL functionality.
Purpose of the Study:
- To investigate the relationship between the acute-phase inflammatory response (APR) and high-density lipoprotein (HDL) structure and function in STEMI patients.
- To evaluate the capacity of HDL to activate endothelial NO synthase (eNOS) in STEMI patients with varying levels of inflammation.
Main Methods:
- Stratified 45 STEMI patients into quartiles based on C-reactive protein (CRP) delta levels (APR peak).
- Assessed HDL structure and its capacity to stimulate nitric oxide (NO) production at admission and APR peak.
- Analyzed the content of paraoxonase-1 (PON-1) and sphingosine-1-phosphate (S1P) in HDL.
Main Results:
- STEMI patients with low APR maintained preserved HDL structure and eNOS activation capacity.
- Patients with significant APR exhibited compromised HDL ability to stimulate eNOS and promote NO production, with particle remodeling.
- Reduced PON-1 and S1P content contributed to the defective NO-stimulating capacity of HDL in high APR patients.
- HDL's cholesterol efflux capacity remained preserved irrespective of the inflammatory response.
Conclusions:
- Only STEMI patients with a significant inflammatory response display HDL defective in stimulating eNOS and NO production.
- These findings extend previous research on impaired HDL function in acute coronary syndrome (ACS).
- The inflammatory response critically influences HDL's protective vascular functions in STEMI.
Aims:
The aim of the present study was to evaluate the high-density lipoprotein (HDL) structure and endothelial NO synthase (eNOS) activation capacity in ST-elevation myocardial infarction (STEMI) patients with different acute-phase inflammatory response (APR).
Methods And Results:
Forty-five STEMI patients were stratified in quartiles according to the delta CRP level, calculated by subtracting the CRP value at admission from the CRP peak value (APR peak). The HDL structure and HDL capacity to stimulate NO production were evaluated at admission and at APR peak. STEMI patients with a low APR had a completely preserved HDL structure and HDL ability to activate eNOS and promote NO production, which did not change during STEMI. On the contrary, HDL from STEMI patients developing a significant APR had compromised ability to stimulate eNOS and promote NO production, and underwent a significant particle remodelling during STEMI. The defective capacity to stimulate NO production of HDL isolated from STEMI patients with high APR was explained, at least in part, by the reduced PON-1 and S1P content. The HDL ability to promote cell cholesterol efflux through different pathways was preserved in ACS patients independently of the inflammatory response.
Conclusion:
The present results extend previous studies reporting an impaired eNOS-activating capacity of HDL from ACS patients, showing that only a subset of patients undergoing STEMI, and in particular those developing an important inflammatory response, have circulating HDL defective in stimulating endothelial eNOS and NO production.
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