Review
Health Care Sciences & Services
Zhuangzhuang Jia, Shuai Wang, Haifeng Yan, Yawen Cao, Xuan Zhang, Lin Wang, Zeyu Zhang, Shanshan Lin, Xianliang Wang, Jingyuan Mao
Summary: Pulmonary vascular remodeling, involving changes in the intima, media and adventitia, is a critical structural alteration and pathological feature in pulmonary hypertension. It includes the proliferation and phenotypic transformation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), as well as interactions with pulmonary artery fibroblasts (PAFs) and extracellular matrix (ECM). Inflammatory mechanisms, apoptosis, and other factors are influenced by different mechanisms that contribute to disease progression. This article reviews these pathological changes and discusses the underlying mechanisms in the remodeling process.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jinjin Pan, Rui Wang, Yandong Pei, Dingyou Wang, Na Wu, Yuke Ji, Qing Tang, Liang Liu, Ke Cheng, Qiwang Liu, Jian Sun, Miaomiao Gong, Xu Zheng, Junxia Li, Changlin Zhang, Yuhui Yuan
Summary: This study aimed to investigate the effect and mechanism of sulforaphane (SFN) on hypoxic pulmonary hypertension (HPH). The results showed that SFN could inhibit the progression of HPH, reduce inflammation and oxidative stress, and promote apoptosis in pulmonary artery smooth muscle cells (PASMCs) under hypoxia conditions. SFN also prevented the apoptosis of pulmonary microvascular endothelial cells (ECs). These findings suggest that SFN has potential therapeutic effects on HPH by improving pulmonary vascular remodeling.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Yu Wang, Zhenyu Zeng, Zhaoxiang Zeng, Guojun Chu, Xinghua Shan
Summary: This study found that CHCHD4 is significantly downregulated in hypoxic PASMCs and lung tissues from hypoxic PAH rats. AAV1-induced CHCHD4 elevation can alleviate vascular remodeling and pulmonary artery resistance, and regulate mitochondrial oxidative phosphorylation in PASMCs. Furthermore, CHCHD4 can modulate mitochondrial dynamics by directly interacting with SAM50 on the mitochondrial outer membrane surface. The expression of CHCHD4 can disturb hypoxic PAH, making it a promising therapeutic target for PAH treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyu Fang, Min Xie, Xiansheng Liu, Yuanzhou He
Summary: High expression of CENPE is observed in PH patients and hypoxia-induced PH animals, and its deficiency inhibits pulmonary vascular remodeling and right ventricular hypertrophy. CENPE may exert its biological effect by targeting the transcription of CDK1 proteins.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Ya Lu, Dongyan Li, Lina Shan
Summary: The present study found that miRNA153 inhibits pulmonary hypertension by promoting apoptosis and inhibiting proliferation of PASMCs. The NFATc3/Kv1.5 channel pathway may be involved in this process.
CLINICAL AND EXPERIMENTAL HYPERTENSION
(2022)
Article
Cell Biology
Yu Zhang, Moises Hernandez, Jonathan Gower, Nolan Winicki, Xena Morataya, Sebastian Alvarez, Jason X-J Yuan, John Shyy, Patricia A. Thistlethwaite
Summary: This study found that the NOTCH3 pathway plays a crucial role in controlling vascular smooth muscle cell proliferation and differentiation in the pulmonary arterial tree. In pulmonary arterial hypertension (PAH) patients, JAGGED-1 is overexpressed in small pulmonary artery smooth muscle cells and selectively activates NOTCH3 signaling, leading to increased cellular proliferation. On the other hand, DELTA-LIKE 4 inhibits NOTCH3 signaling and retards smooth muscle cell proliferation. A new monoclonal antibody was developed to block JAGGED-1-induced cleavage of NOTCH3 and successfully reversed pulmonary hypertension in animal models without toxic side effects. Targeting JAGGED-1 activation of NOTCH3 may be an effective and safe strategy for treating PAH.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Pei-Ling Chi, Chin-Chang Cheng, Cheng-Chung Hung, Mei-Tzu Wang, Hsien-Yueh Liu, Meng-Wei Ke, Min-Ci Shen, Kun-Chang Lin, Shu-Hung Kuo, Pin-Pen Hsieh, Shue-Ren Wann, Wei-Chun Huang
Summary: This study found that levels of MMP-1 and MMP-10 were increased in the vessel wall, serum, and M1-polarized macrophages of PAH patients and PAH rodent models. MMP-10 promotes the malignant phenotype of PASMCs by promoting their proliferation and migration. Inhibition of STAT1 can suppress hypoxia-induced MMP-10 expression in M1-polarized macrophages.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Charifa Awada, Alice Bourgeois, Sarah-Eve Lemay, Yann Grobs, Tetsuro Yokokawa, Sandra Breuils-Bonnet, Sandra Martineau, Vinod Krishna, Francois Potus, Jey Jeyaseelan, Steeve Provencher, Sebastien Bonnet, Olivier Boucherat
Summary: Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling, and the inhibition of the histone methyltransferase G9a/GLP may represent a new therapeutic approach for PAH.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaowei Nie, Chenyou Shen, Jianxin Tan, Xusheng Yang, Wei Wang, Youai Dai, Haijian Sun, Zhiyuan Wu, Jingyu Chen
Summary: The study demonstrated that Andrographolide (ANDRO) may reverse pulmonary vascular remodeling through modulation of NOX/Nrf2-mediated oxidative stress and NF-kappa B-mediated inflammation, suggesting therapeutic potential in the treatment of pulmonary hypertension.
Review
Cell Biology
Qiang Zhao, Ping Song, Ming-Hui Zou
Summary: Pulmonary hypertension is a debilitating disease characterized by increased blood pressure in the pulmonary arteries. The role of AMPK in PH is controversial as both inhibition and activation of AMPK can potentially prevent the development of PH. Clinical studies suggest that metformin, an AMPK activator, is effective in treating early-stage PH and particularly beneficial for patients with PH associated with heart failure.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Critical Care Medicine
Bradley A. Maron, David E. Kleiner, Elena Arons, Bradley M. Wertheim, Nirmal S. Sharma, Kathleen J. Haley, Andriy O. Samokhin, Ethan J. Rowin, Martin S. Maron, Douglas R. Rosing, Barry J. Maron
Summary: This study found that in patients with hypertrophic cardiomyopathy (HCM), the interpretation of pulmonary hypertension (PH) pathophysiological features may be confounded by dynamic left ventricular outflow tract obstruction. By comparing multiple HCM patients and control tissue specimens, the study found that HCM patients exhibited pulmonary arterial hypertrophy and fibrosis, which correlated with myocardial thickness and left ventricular outflow tract gradient. These findings have important implications for understanding the PH pathophysiological features in HCM patients.
Article
Geriatrics & Gerontology
Wen Zhang, Wenchao Lin, Xiaofang Zeng, Mengqiu Zhang, Qin Chen, Yiyang Tang, Jing Sun, Benhui Liang, Lihuang Zha, Zaixin Yu
Summary: This study explored the role of core fucosylation and the glycosyltransferase FUT8 in pulmonary arterial hypertension (PAH). The increased core fucosylation observed in PAH rat models and isolated rat pulmonary artery smooth muscle cells (PASMCs) was inhibited by 2-fluorofucose (2FF), which improved hemodynamics and pulmonary vascular remodeling. FUT8 expression and concentration were found to be elevated in PAH patients, and knockdown of FUT8 alleviated the phenotypic changes in PASMCs induced by PDGF-BB. FUT8 activated the AKT pathway and its effects on PASMCs could be partially counteracted by an AKT activator.
Article
Cardiac & Cardiovascular Systems
Rui Wang, Jinjin Pan, Jinzhen Han, Miaomiao Gong, Liang Liu, Yunlong Zhang, Ying Liu, Dingyou Wang, Qing Tang, Na Wu, Lin Wang, Jinsong Yan, Hua Li, Yuhui Yuan
Summary: This study demonstrates that melatonin can alleviate dasatinib-aggravated hypoxic pulmonary hypertension by inhibiting pulmonary vascular remodeling and protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Integrative & Complementary Medicine
Ling Chen, Liquan Ren, Hongping Song, Hui Ren, Rong Xu, Xuying Huang
Summary: The study investigated the protective effects of triflavones from Selaginella doederleini against pulmonary hypertension (PH) in a rat model. Triflavones effectively reduced mPAP and arterial thickness, reversed increased proliferation and inhibited apoptosis induced by chronic hypoxia, and exhibited inhibitory effects on vascular remodeling through the PI3K/Akt signaling pathway.
ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Ning Huang, Tian-Tian Zhu, Ting Liu, Xiao-Yue Ge, Di Wang, Hong Liu, Guang-Xuan Zhu, Zheng Zhang, Chang-Ping Hu
Summary: Pulmonary vascular remodeling is the pathological basis of pulmonary hypertension, with Endothelial-to-mesenchymal transition playing a key role in its pathogenesis. Aspirin, through inhibiting the HIF-1 alpha/TGF-beta 1/Smads/Snail signaling pathway, shows promise in ameliorating PVR in hypoxia-induced PH, suggesting it as a potential therapeutic option for patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
