Page 141 - Assessing right ventricular function and the pulmonary circulation in pulmonary hypertension Onno Anthonius Spruijt

from 5 IPAH patients and 5 donor lungs in culture. IPAH pulmonary fibroblasts demonstrated increased expression of ENT1, TP and TK1 in comparison to control donor cells (Figure 2).
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0 Donor IPAH
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ENT1 TK1
TP
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Figure 2. Pulmonary artery adventitial fibroblasts isolated from lungs of patients with idiopathic pulmonary arterial hypertension (IPAH) exhibited increased expressions of ENT1, TK1 and TP in transcription level compared with cells from donor lungs. Data are expressed as mean±SEM; n≥6 in each group. **P<0.01 , *P<0.05.
Increased Lung 18FLT Uptake in a MCT PAH Model
To interpret the relationship between lung 18FLT uptake and the underlying pulmonary vascular pathology, further studies were conducted in the MCT PAH rat. Static images obtained from 60 min dynamic PET acquisitions demonstrated significantly higher accumulation of 18FLT in the MCT rat lung (Figure 3A); 18FLT SUV in the 4 week MCT group was >50% greater than in the control group (Supplement Figure II). Dynamic 60 min PET data acquisition was used for kinetic modeling using a 2T4K compartmental model. There was a progressive increase in 18FLT phosphorylation (k3) (Figure 3B) as well as overall 18FLT influx rate (Ki) (Supplement Figure II) in MCT rat lungs, supported by direct tissue 18FLT measurements (Figure 3C).
Histological examination of the MCT lung showed progressive vascular remodeling over 1 and 4 weeks post MCT injection as previously demonstrated [9].The remodeled vessels in the MCT rat lung demonstrated Ki67 expression (Figure 3D), as well as prominent ENT1 and TK1 expression (Figure 3F). The increased phosphorylation rate (k3) in MCT rats was in proportion to the vascular pathology and closely correlated (r2=0.78, P> .0001) with the Ki‐67 score (Figure 3E).
Attenuated Lung 18FLT Uptake with Imatinib and DCA Treatment in the MCT Model
We investigated the response of 18FLT PET measurements to treatments with proven anti‐ proliferative efficacy in the MCT rat model. Treatment with DCA or imatinib during weeks 2 to 4 post MCT attenuated pulmonary vascular remodelling, as demonstrated by significant reductions in the
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Relative mRNA expression ENT
Relative mRNA expression TK1
Relative mRNA expression TP