Aghajani Nargesi, Arash

Background: Scattered tubular-like cells (STCs) proliferate and differentiate to support neighboring injured renal tubular cells during recovery from insults. Renal artery stenosis (RAS) induces renal ischemia and hypertension and leads to loss of kidney function, but whether RAS alters renal endogenous repair mechanisms, such as STCs, remains unknown. We hypothesize that RAS in swine modifies the messenger RNA (mRNA) profile of STCs, blunting their in vitro reparative capacity. Methods: CD24+/CD133+ STCs were isolated from pig kidneys after 10-weeks of RAS or sham (n = 3 each) and their gene cargo analyzed using high-throughput mRNAseq. Expression profiles for upregulated and downregulated mRNAs in RAS-STCs were functionally interpreted by gene ontology analysis. STC activation was assessed by counting the total number of STCs in pig kidney sections using flow cytometry, whereas cell proliferation was assessed in vitro. Results: Of all expressed genes, 1430 genes were upregulated and 315 downregulated in RAS- versus Normal-STCs. Expression of selected candidate genes followed the same fold change directions as the mRNAseq findings. Genes upregulated in RAS-STCs were involved in cell adhesion, extracellular matrix remodeling, and kidney development, whereas those downregulated in RAS-STCs are related to cell cycle and cytoskeleton. The percentage of STCs from dissociated kidney cells was higher in RAS versus Normal pigs, but their proliferation rate was blunted. Conclusions: Renal ischemia and hypertension in swine induce changes in the mRNA profile of STCs, associated with increased STC activation and impaired proliferation. These observations suggest that RAS may alter the reparative capacity of STCs.

AbstractAimAchieving the optimal apposition of coronary stents during percutaneous coronary intervention is not always feasible. The risks and benefits of stent postdilation in primary percutaneous coronary intervention (PPCI) in patients with ST‐elevation myocardial infarction (STEMI) have remained controversial. We sought to evaluate the immediate angiographic and long‐term outcomes in patients with and without stent postdilation.MethodsA cohort of patients (n = 1,224) with STEMI, treated with PPCI (n = 500 postdilated; n = 724 controls), were studied. The flow grade, the myocardial blush grade, and the frame count were considered angiographic outcomes. The clinical outcomes were major adverse cardiovascular events (MACE)—comprising cardiac death, nonfatal MI, and repeat revascularization—and the device‐oriented composite endpoint (DOCE)—consisting of cardiac death, target lesion revascularization, and target vessel revascularization.ResultsThe flow and myocardial blush grades were not different between the two groups, and the frame count was significantly lower in the postdilation group (15.7 ± 8.4 vs. 17 ± 10.4; p < .05). The patients were followed up for 348 ± 399 days. DOCE (2.2% vs. 5.8%) and cardiac mortality (1.2% vs. 3.2%) were lower in the postdilation group. In the fully adjusted propensity score‐matched analysis, postdilation was associated with decreased DOCE (HR = 0.40 [0.18–0.87], p = .021).ConclusionsSelective postdilation improved some angiographic and clinical outcomes and could not be discouraged in PPCI on patients with STEMI.