4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats
| Autor: | Lei-Qi Wu, Ming-Yuan Li, Alidan Aierken, Fen Liu, Mei Long, Jie Wang, Yun Wu, Yi-Tong Ma, Minawaer Hujiaaihemaiti, Min-Tao Gai, Dilare Adi, Qian Li |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology Gene Expression lcsh:Medicine Hemodynamics Apoptosis Blood Pressure 030204 cardiovascular system & hematology Pharmacology Endoplasmic Reticulum Pathology and Laboratory Medicine Vascular Medicine Biochemistry Random Allocation eIF-2 Kinase 0302 clinical medicine Cell Signaling Medicine and Health Sciences Pulmonary Arteries lcsh:Science Immune Response Heat-Shock Proteins Monocrotaline Secretory Pathway Multidisciplinary Cell Death Reverse Transcriptase Polymerase Chain Reaction Arteries Endoplasmic Reticulum Stress Phenylbutyrates Signaling Cascades Cell Processes Ventricular pressure Anatomy Cellular Structures and Organelles Research Article Signal Transduction medicine.medical_specialty Hypertension Pulmonary Blotting Western Immunology Antineoplastic Agents Pulmonary Artery Protective Agents Phenylbutyrate Stress Signaling Cascade 03 medical and health sciences Signs and Symptoms Diagnostic Medicine medicine.artery DNA-binding proteins parasitic diseases Genetics medicine Animals Humans Gene Regulation Rats Wistar Ventricular remodeling Inflammation business.industry lcsh:R Biology and Life Sciences Proteins Cell Biology medicine.disease Pulmonary hypertension Chaperone Proteins Regulatory Proteins Disease Models Animal 030104 developmental biology Blood pressure Pulmonary artery Cardiovascular Anatomy Unfolded protein response Blood Vessels lcsh:Q business Transcription Factors |
| Zdroj: | PLoS ONE, Vol 11, Iss 6, p e0157538 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0157538 |
| Popis: | Background Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. Methods and Results Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. Conclusion Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries. |
| Databáze: | OpenAIRE |
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