CCL5 deficiency rescues pulmonary vascular dysfunction, and reverses pulmonary hypertension via caveolin-1-dependent BMPR2 activation

Nie, Xiaowei; Tan, Jianxin; Dai, Youai; Liu, Yun; Zou, Jian; Sun, Jie; Ye, Shugao; Shen, Chenyou; Fan, Li; Chen, Jingyu; Bian, Jin-Song

doi:10.1016/j.yjmcc.2018.01.016

Cited by 41 publications

(32 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In sugen + hypoxia model (mice), the deletion of CCL5 resulted in reduction in PH via caveolin-1-dependent amplification of BMPR2 signaling. It stabilized surface caveolin-1, restored BMPR2 signaling and enhanced BMPR2 and caveolin-1 interaction [24]. This observation further supports the role for inflammation in PH.…”

Section: Pulmonary Hypertensionsupporting

confidence: 72%

Endothelial Dysfunction and Disruption in Pulmonary Hypertension

Mathew¹

2021

Cardiovascular Risk Factors in Pathology

View full text Add to dashboard Cite

A number of systemic diseases lead to pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate. Irrespective of the underlying disease, endothelial dysfunction or disruption plays a key role in the initiation and progression of PH. Endothelial dysfunction and disruption result in impaired vascular relaxation response, activation of proliferative pathways leading to medial hypertrophy and PH. Endothelial cells (EC) play a crucial role in regulating vascular tone and maintaining homeostasis. Caveolin-1, a 21-22 kD membrane protein, interacts with a number of transducing factors and maintains them in a negative conformation. Disruption of EC results in endothelial caveolin-1 loss and reciprocal activation of proliferative pathways leading to PH, and the accompanying loss of PECAM1 and vascular endothelial cadherin results in barrier dysfunction. These changes lead to the irreversibility of PH. Hypoxia-induced PH is not accompanied by endothelial disruption or caveolin-1 loss but is associated with caveolin-1 dysfunction and the activation of proliferative pathways. Removal of hypoxic exposure results in the reversal of the disease. Thus, EC integrity is an important factor that determines irreversibility vs. reversibility of PH. This chapter will discuss normal EC function and the differences encountered in PH following EC disruption and EC dysfunction.

show abstract

Section: Pulmonary Hypertensionsupporting

confidence: 72%

Endothelial Dysfunction and Disruption in Pulmonary Hypertension

Mathew¹

2021

Cardiovascular Risk Factors in Pathology

View full text Add to dashboard Cite

show abstract

“…Interestingly, deletion of Ccl5 has been shown to attenuate Sugen-hypoxia model of PH via Cav1dependent amplification of Bmpr2 signaling [47]. As presented in Fig.…”

Section: Discussionmentioning

confidence: 88%

Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

Mathew

Huang

Iacobaş

et al. 2019

Preprint

View full text Add to dashboard Cite

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), lung histology and transcriptomes of six weeks old male rats with PH induced by: 1) hypoxia (HO), 2) administration of monocrotaline (CM) or 3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations and also neointimal lesions and obliteration of lumen in small arteries. We found that the PH increased the expression of caveolin1, matrix metallopeptidase 2 and numerous inflammatory and cell proliferation genes. The cell-cycle, vascular smooth muscle contraction and the oxidative phosphorylation pathways, as well as their interplay were largely perturbed. Our results also suggest that the up-regulated Rhoa (ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed especially in HM group, indicate metabolic shift towards aerobic glycolysis.

show abstract

“…Like CCL5, CCR5 content is also increased in PAH in several cell types that display up-regulated CCR5 expression, including PASMCs, PAECs, and macrophages (Amsellem et al, 2014;Nie et al, 2018).…”

Section: Ccl5/ccr5/ccr1mentioning

confidence: 99%

The role of chemokines and chemokine receptors in pulmonary arterial hypertension

Mamazhakypov

Viswanathan

Lawrie

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary artery remodelling leading to increased right ventricular pressure overload, which results in right heart failure and premature death. Inflammation plays a central role in the development of PAH, and the recruitment and function of immune cells are tightly regulated by chemotactic cytokines called chemokines. A number of studies have shown that the development and progression of PAH are associated with the dysregulated expression of several chemokines and chemokine receptors in the pulmonary vasculature. Moreover, some chemokines are differentially regulated in the pressure-overloaded right ventricle. Recent studies have tested the efficacy of pharmacological agents targeting several chemokines and chemokine receptors for their effects on the development of PAH, suggesting that these receptors could serve as useful therapeutic targets. In this review, we provide recent insights into the role of chemokines and chemokine receptors in PAH and RV remodelling and the opportunities and roadblocks in targeting them.

show abstract

CCL5 deficiency rescues pulmonary vascular dysfunction, and reverses pulmonary hypertension via caveolin-1-dependent BMPR2 activation

Cited by 41 publications

References 60 publications

Endothelial Dysfunction and Disruption in Pulmonary Hypertension

Endothelial Dysfunction and Disruption in Pulmonary Hypertension

Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

The role of chemokines and chemokine receptors in pulmonary arterial hypertension

Contact Info

Product

Resources

About