Comparison of lung proteome profiles in two rodent models of pulmonary arterial hypertension.
We studied the lung proteome changes in two widely used models of pulmonary arterial hypertension (PAH): monocrotaline (MCT) injection and chronic hypoxia (CH); untreated rats were used as controls (n = 6/group). After 28 days, invasive right ventricular systolic pressure (RVSP) was measured. Lungs were immunostained for alpha-smooth muscle actin (alphaSMA). 2-DE (n = 4/group) followed by nano-LC-MS/MS was applied for protein identification. Western blotting was used additionally if possible. RVSP was significantly increased in MCT- and CH-rats (MCT 62.5 +/- 4.4 mmHg, CH 62.2 +/- 4.1 mmHg, control 25.0 +/- 1.7 mmHg, p<0.001). This was associated with an increase of alphaSMA positive vessels. In both groups, there was a significantly increased expression of proteins associated with the contractile apparatus (diphosphoHsp27 (p<0.001), Septin2 (p<0.001), F-actin capping protein (p<0.01), and tropomyosin beta (p<0.02)). In CH, proteins of the nitric oxide (Hsc70; p = 0.002), carbon monoxide (biliverdin reductase; p = 0.005), and vascular endothelial growth factor (VEGF) pathway (annexin 3; p<0.001) were significantly increased. In MCT, proteins involved in serotonin synthesis (14-3-3; p = 0.02), the enhanced unfolded protein response (ERp57; p = 0.02), and intracellular chloride channels (CLIC 1; p = 0.002) were significantly elevated. Therefore, MCT- and CH-induced vasoconstriction and remodeling seemed to be mediated via different signaling pathways. These differences should be considered in future studies using either PAH model.
Laudi
Sven
S
University of Leipzig Medical Faculty, Department of Anesthesiology and Intensive Care Medicine, Leipzig, Germany. sven.laudi@medizin.uni-leipzig.de
Steudel
Wolfgang
W
Jonscher
Karen
K
Schöning
Wenzel
W
Schniedewind
Björn
B
Kaisers
Udo
U
Christians
Uwe
U
Trump
Saskia
S
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D020543:Proteome / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D020543:Proteome; D016686:Monocrotaline