Selenoprotein P in Myocardial Infarction With Cardiogenic Shock

Abstract

Background: Reperfusion strategies in acute myocardial infarction (AMI) may result in ischemia reperfusion injury characterized by increased oxidative stress, inflammation, and ultimately death of myocardial tissue which may be of particular importance in infarct-related cardiogenic shock (CS). Many anti-oxidative and immune regulatory processes depend on selenium which in large proportions is bound to circulating selenoprotein P (SelP). Individual SelP patterns may therefore be associated with inflammatory response and possibly mortality in patients with CS post AMI. Methods: In the randomized Intra-Aortic Balloon Pump in cardiogenic Shock II (IABP-SHOCK II)-trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. In a predefined biomarker substudy of 147 patients, we analyzed SelP levels 1 and 3 days following randomization. Samples were compared with healthy controls and associations with the unspecific inflammatory marker C-reactive protein (CRP) were analyzed. Results: Compared with controls SelP levels in patients with infarct-related CS were markedly higher (2.7-fold at day 1 and 5.7-fold at day 3 following AMI, all P < 0.001). Thirty-day mortality was significantly higher in patients with SelP levels above the 75th percentile at day 3 following AMI (26% vs. 46%, P = 0.045). SelP was significantly proportionally correlated with CRP 1 (R2 = 0.762, P < 0.0001) and 3 days (R2 = 0.777 P < 0.0001) following AMI. Conclusion: SelP levels are significantly increased post AMI with CS. Higher SelP levels are associated with increased CRP levels indicative for inflammatory processes. Future studies should focus on the characterization of SelP profiles following AMI and the identification of pathomechanisms affected by SelP.

The Impact of Selenium Deficiency on Cardiovascular Function

“…Low SELENOP levels are associated with increased risk of mortality in acute heart failure patients and all-cause cardiovascular mortality [ 77 , 78 ]. A decrease in circulating levels of SELENOP was also associated with a greater risk of metabolic syndrome in patients with documented cardiovascular disease [ 79 ]. Despite this clinical association, it is unclear if SELENOP is indeed necessary to prevent cardiovascular disease, as SELENOP KO mice subjected to I/R injury exhibited significantly reduced infarct sizes, indicating that less tissue was damaged, and cardiac apoptosis compared to WT mice.…”

The Gut Microbiome, Seleno-Compounds, and Acute Myocardial Infarction

“…As mentioned above, selenoproteins, especially GPX and TrxR, regulate the oxidative balance of target organs within the human body [ 30 , 36 ]. In reaction to AMI events, the levels of selenoproteins in the serum increase and are positively correlated with the severity of the AMI [ 37 , 38 ]. Therefore, selenium administration after myocardial infarction could enhance ROS neutralization and decrease cardiac injury [ 37 ].…”

“…In reaction to AMI events, the levels of selenoproteins in the serum increase and are positively correlated with the severity of the AMI [ 37 , 38 ]. Therefore, selenium administration after myocardial infarction could enhance ROS neutralization and decrease cardiac injury [ 37 ]. Previously, serum and urine selenium concentrations in AMI patients have been declared to be significantly lower than those found in the control group [ 39 ].…”

Increases in Hepatokine Selenoprotein P Levels Are Associated With Hepatic Hypoperfusion and Predict Adverse Prognosis in Patients With Heart Failure

“… 1 , 4 Elevated levels of selenoprotein P may not simply be attributable to hepatocyte cell death, as the level was not correlated with liver enzymes such as aspartate aminotransferase in the present study. An observational study reported that selenoprotein P levels were elevated in cardiogenic shock after acute myocardial infarction and that hemodynamic changes, particularly anti‐inflammatory processes resulting from organ hypoperfusion, may contribute to the increased expression of selenoprotein P. 24 Intermittent hypoxia was reported to transcriptionally upregulate selenoprotein P expressions in cultured human hepatocyte cell lines. 25 Decreased resting cardiac output may be predominantly an issue in patients with HF with reduced LVEF, but selenoprotein P levels did not differ among the different HF phenotypes such as stratification by LVEF.…”