Interrogating Cardio-Renal Crosstalk After Acute Myocardial Infarction by Use of TSPO-Targeted PET/CT

Ziel/Aim The 18kD mitochondrial translocator protein (TSPO) is physiologically expressed in kidneys, myocardium and immune cells, where it contributes to the cellular stress response. Here, we used whole-body, targeted PET for obtaining insights into TSPO pathology in heart and kidneys, and their interrelation, following myocardial infarction (MI).

Methodik/Methods C57Bl6 mice underwent coronary artery ligation (n = 17) or sham surgery (n = 9). Serial PET imaging with F-18-GE180 was conducted at 7d, 4 wk, and 8 wk to assess TSPO expression in heart and kidneys. A subgroup of MI mice (n = 8) were treated with the angiotensin converting enzyme inhibitor enalapril, which is cardioprotective and regulates TSPO expression in kidneys. Tracer uptake in both organs was evaluated and compared to the time course of left ventricular function.

Ergebnisse/Results TSPO signal was elevated in the infarct territory at 1 wk after coronary ligation, declining by 4 wk and 8 wk ( % injected dose (ID)/g, normalized to perfusion: 9.5 ± 2.6 vs 5.4 ± 2.7* vs 5.4 ± 3.2*, *p < 0.05 to 1 wk). Similarly, renal TSPO signal steadily declined from 1 wk to 8 wk after MI ( %ID/g, 11.3 ± 1.4 vs. 10.1 ± 1.8 vs. 9.2 ± 1.9, n.s.). Tracer uptake in heart and kidneys was directly correlated (r = 0.39, p < 0.05). Early treatment with enalapril spared contractile function at 8 wk after MI compared to untreated mice (28 ± 4  % vs. 48 ± 8  %, P = 0.001). In untreated animals, early renal TSPO signal at week 1 did not correlate significantly with late LVEF at week 8 (R = 0.51, P = 0.2), whereas a significant correlation was observed in animals under enalapril treatment (R = 0.73, P < 0.05), supporting the notion of an effect of enalapril on both heart and kidneys.

Schlussfolgerungen/Conclusions TSPO-targeted PET may allow for monitoring of crosstalk between heart and kidneys after MI. The specific role of TSPO in degeneration and healing of both organs, along with their interaction, warrants further investigation.