Rationale: Type-1 cardio-renal syndrome (CRS) is characterized by an acute kidney dysfunction due to renal arteriolar vasoconstriction following an acute worsening of cardiac function. It is well know that HO-1 upregulation has a cardio protective and renoprotective function mediated by anti-oxidative, anti-inflammatory, anti-apoptotic and vasodilating effects. An alteration of T-lymphocyte-related immune response seems to be one of the potential mechanisms involved in type-1 CRS.
Objective: The aim of this study was to assess 1) if HO-1 upregulation could be a therapeutic target for type 1 CRS and 2) the role of T-lymphocytes in HO-1 induced effects on renal function in type 1 CRS.
Methods: Post-ischemic heart failure was induced by left anterior coronary artery ligation in C57Bl6 and SCID (T lymphocytes deficient) mice. Animals were divided into 4 groups: sham, myocardial infarction (MI), MI treated with HO-1 inducer cobalt protoporphyrin (CoPP) with and without the HO activity inhibitor stannous mesoporphyrin (SnMP). All mice underwent echocardiography (fractional area shortening, FAS) and renal Doppler sonography (intrarenal pulsatility index, PI) 30 days after surgery.
Results: Heart function was significantly reduced in MI groups (C57: FAS: sham 0.36\ub10.06, MI 0.26\ub10.04, p<0.05; SCID: FAS: sham 0.34\ub10.04, MI: 0.24\ub10.04, p<0.01) and PI was significantly increased in MI groups compared to sham groups (C57: PI: sham 0.98\ub10.05, MI: 1.12\ub10.11, p<0.05; SCID: PI: sham 0.72\ub10.08, MI 1.37\ub10.37, p<0.05). HO-1 induction improved heart function in both C57 and SCID mice but only in SCID mice was a significant improvement of renal vasoconstriction observed (SCID; PI: MI+CoPP 0.9\ub10.19 p<0.05). In SCID mice SnMP treatment reversed the effect of CoPP on heart function and renal vasoconstriction.
Conclusion: Our novel study showed that T lymphocyte mediated immunity is involved in type 1 CRS and upregulation of HO-1, in this setting, could be a therapeutic target for improving type 1 CRS.
Author Disclosures: P. Pesce: None. D. Sacerdoti: None. M. Boldrin: None. R. Rezzani: None. N.G. Abraham: None.
Key Words: Renal circulation \u2022 Heart failure \u2022 Immunologic factors \u2022 Oxidative stres
