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Abstract Background Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats. Methods Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45- CD73+ CD90+ MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure. Results A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed in vivo bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group. Conclusion Adhesive BM-derived CD45- CD73+ CD90+ MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions.

Aim: Tunable size ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles from 3 to 9 nm coated with polyethylene glycol phosphonate moieties have been designed for neovascularization MRI. Materials & methods: USPIO were synthesized using a nonaqueous sol-gel method. An ischemia-reperfusion rat model has been chosen for neo-angiogenesis and scanned on MRI after injection of different sized USPIO. Histological studies have been performed for USPIO localization within the tissue. Results: The magnetic properties and consequently their MRI relaxivities are drastically dependent on the crystalline core size. In vivo MRI spots were observed specifically in the ischemic area. The best MRI contrast within neovascularization is generated by 6 nm nanoparticles proving that compromise between T2 relaxivity and physico-chemical properties is essential for the design of effective MRI contrast agent. [ABSTRACT FROM AUTHOR]

Coronary blood flow control is not uniform along the vascular tree and particularly between the right coronary artery and the left anterior descending artery. Resting membrane potential that contributes largely to the vascular tone is mainly regulated by K+ channels in coronary myocytes. In the present study, we hypothesized that right coronary artery (RCA) and left coronary artery (LCA) exhibited a cell-specific function of K+ channels. The net outward current was markedly greater in RCA compared with LCA cells, and this difference was due to a larger 4-aminopyridine (4-AP)-sensitive voltage-gated potssium (Kv) current in RCA cells, whereas the iberiotoxin (IbTx)-sensitive, large conductance Ca2+-dependent potassium (BKCa) current was smaller in RCA cells. To go further in the molecular identity of this Kv current, we used 50 nM correolide, which specifically blocked Kv1 family α-subunits. Outward currents generated by ramp depolarization protocols were highly sensitive to correolide in both RCA and LCA cells, suggesting that Kv1 contributed for a large part to the net outward current. 4-AP-induced contractions in isolated RCA, and LCA were greater than IbTx-induced contraction. Furthermore, the 4-AP-induced contraction in RCA was significantly greater than that in LCA, which is in agreement with the electrophysiological data. Finally, the Kv1.2 α-subunit but not the Kv1.5 was detected in both RCA and LCA using primary specific antibody in Western blotting and immunofluorescence assay, and expression of Kv1.2 α-subunit was markedly higher in RCA compared with LCA. In summary, we reported for the first time a heterogeneous function and expression of Kv1 α-subunits in rat coronary myocytes isolated from RCA or LCA. [ABSTRACT FROM AUTHOR]

Aim: Tunable size ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles from 3 to 9 nm coated with polyethylene glycol phosphonate moieties have been designed for neovascularization MRI., Materials & Methods: USPIO were synthesized using a nonaqueous sol-gel method. An ischemia-reperfusion rat model has been chosen for neo-angiogenesis and scanned on MRI after injection of different sized USPIO. Histological studies have been performed for USPIO localization within the tissue., Results: The magnetic properties and consequently their MRI relaxivities are drastically dependent on the crystalline core size. In vivo MRI spots were observed specifically in the ischemic area. The best MRI contrast within neovascularization is generated by 6 nm nanoparticles proving that compromise between T 2 relaxivity and physico-chemical properties is essential for the design of effective MRI contrast agent.

The purpose of this study was to evaluate the reversibility of right ventricular (RV) remodelling after pulmonary artery hypertension (PAHT) secondary to 3 wk of hypobaric hypoxia. A group of 10 adult male Wistar rats were studied and were the following: control normoxic (C), after 3 wk of chronic hypoxia (CH), and after 3 wk of exposure to hypoxia followed by 3 wk of normoxia recovery (N-RE). Mean pulmonary artery pressure was 11 +/- 2 mmHg in the C group, 35 +/- 2 mmHg in the CH group, and 14 +/- 3 mmHg in the N-RE group. RV function was assessed by echocardiography. In the CH group, the pulmonary flow measured in Doppler mode depicted a midsystolic notch and a decrease of the pulmonary acceleration time compared with control [17 +/- 1 vs. 34 +/- 1 ms (n = 10), respectively; P < 0.05]. RV thickening measured in M-mode was apparent in the CH group compared with the control group [2.84 +/- 0.40 vs. 1.73 +/- 0.26 mm (n = 10), P < 0.05]. In the N-RE group, the RV wall was significantly thinner compared with the CH group [1.56 +/- 0.08 vs. 1.73 +/- 0.26 mm (n = 10), P < 0.05]. The calculated RV diameter shortness fraction was not different between the CH group and C group (34 +/- 4.2% vs. 36 +/- 2.8%) but decreased in the N-RE group [20 +/- 2.4% (n = 10), P < 0.01]. The E-to-A wave ratio on the tricuspid Doppler inflow was significantly lower in the CH group and N-RE group compared with the C group [0.70 +/- 0.8 and 0.72 +/- 0.1 vs. 0.88 +/- 0.2 (n = 10), respectively; P < 0.05]. In the isolated perfused heart using the Langendorff method, RV compliance was increased in the CH group and decreased in the N-RE group. In the N-RE group, fibrous bands with metaplasia were observed on histological sections of the RV free wall. We conclude that PAHT induces nonreversible RV dysfunction with dysplasia.