Endothelial fate mapping in mice with pulmonary hypertension.

BACKGROUND: Pulmonary endothelial injury triggers a reparative program, which in susceptible individuals is characterized by neointima formation, vascular narrowing, and the development of pulmonary arterial hypertension. The neointimal cells in human pathological plexiform lesions frequently coexpress smooth muscle α-actin and the endothelial von Willebrand antigen, creating a question about their cellular lineage of origin. METHODS AND RESULTS: Experimental pulmonary hypertension with neointima formation develops in C57Bl/6 mice subjected to left pneumonectomy followed 1 week later by jugular vein injection of monocrotaline pyrrole (20 µg/µL and 1 µL/g; group P/MCTP). Compared with the group vehicle, by day 35, group P/MCTP developed higher right ventricular systolic pressure (54±5 versus 25±2 mm Hg; P<0.01) and right ventricular hypertrophy (0.58±0.16 versus 0.26±0.05; P<0.01). Transgenic vascular endothelial-cadherin Cre recombinase or Tie-2 Cre mice were intercrossed with mTomato/mGreen fluorescent protein double-fluorescent Cre reporter mice to achieve endothelial genetic lineage marking with membrane-targeted green fluorescent protein. In control mice, few endothelial lineage-marked cells lining the lumen of small pulmonary arteries demonstrate expression of smooth muscle α-actin. Concurrent with the development of pulmonary hypertension, endothelial lineage-marked cells are prominent in the neointima and exhibit expression of smooth muscle α-actin and smooth muscle myosin heavy chain. Human pulmonary arterial hypertension neointimal lesions contain cells that coexpress endothelial CD31 or von Willebrand antigen and smooth muscle α-actin. CONCLUSION: Neointimal cells in pulmonary hypertension include contributions from the endothelial genetic lineage with induced expression of smooth muscle α-actin and smooth muscle myosin heavy chain.

Eating is a protected behavior even in the face of persistent pain in male rats.

Feeding is critical for survival. Yet, patients with chronic pain often lose their appetite and eat less. We previously showed that ad libitum fed male rats continue to feed rather than withdraw from a brief noxious stimulus. This study examined the effects of a sustained noxious stimulus on feeding by testing ad libitum fed male rats for five eating behaviors--latency to eat, time taken to eat each chip, pauses and scanning during eating, and the number of chocolate chips eaten--during the hour following a sham injection or an injection of a low (0.5%) or moderate (1.5%) dose of formalin into the hind paw. Sham-injected rats showed no pain-related behaviors, rats injected with 0.5% formalin showed very few pain-related behaviors, and rats injected with 1.5% formalin showed favoring, lifting and licking of the injured paw with a characteristic biphasic time course. Besides taking less time to commence eating during the first phase of formalin pain, rats injected with either dose of formalin did not differ from sham-injected rats on any of the other eating measures. Rats injected with 0.5% formalin showed no pain behaviors during eating, whereas those given 1.5% formalin typically ate while not exhibiting any pain behaviors but occasionally ate while favoring the paw, rarely while lifting the paw, and never while licking the paw. These results show that eating is a protected activity even in the presence of persistent pain in male rats.