Pulmonary Arterial Hypertension: Pathophysiology and Treatment

Lan, Norris S H; Massam, Benjamin D; Kulkarni, Sandeep S.; Lang, Chim C.

doi:10.3390/diseases6020038

Cited by 103 publications

(109 citation statements)

References 102 publications

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“…This may confirm the hypothesis that impaired level of adipose tissue factors influences also endothelial dysfunction and aberrant angiogenesis which is one of the main features of SSc. The excess of circulating endothelin-1 may be the cause of micro-and macrovascular changes and their further complications such as digital ulcers formation and pulmonary arterial hypertension frequently observed in SSc patients [22]. It should be also emphasized that an initial vascular injury results in an exacerbated inflammatory response which finally promotes fibrosis [23].…”

Section: Discussionmentioning

confidence: 99%

Altered serum level of metabolic and endothelial factors in patients with systemic sclerosis

et al. 2019

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Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by progressive fibrosis, vascular impairment and immune abnormalities. In recent years, adipokines (mediators synthetized by adipose tissue) have been indicated as a possible missing link in the pathogenesis of SSc. The aim of this study was to investigate the serum concentration of metabolic adipose tissue factors: adiponectin, resistin, leptin and endothelial proteins: endothelin-1, fractalkine and galectin-3 in patients with systemic sclerosis. The study included 100 patients with confirmed SSc diagnosis and 20 healthy individuals. The concentration of respective proteins was determined by enzyme-linked immunosorbent assay. The following markers showed statistically significant increased mean concentrations in patients with SSc in comparison to healthy control: resistin (13.41 vs 8.54 ng/mL; P = 0.0012), endothelin-1 (1.99 vs 1.31 pg/mL; P = 0.0072) and fractalkine (2.93 vs 1.68 ng/mL; P = 0.0007). Elevated serum levels of galectin-3 (4.54 vs 3.26 ng/mL; P = 0.0672) and leptin (19,542 vs 14,210 pg/mL; P = 0.1817) were observed. Decreased concentration of adiponectin was found in patients with SSc (5150 vs 8847 pg/mL; P = 0.0001). Fractalkine and galectin-3 levels were significantly higher in diffuse cutaneous SSc than limited cutaneous SSc subset (3.93 ng/mL vs 2.58 ng/mL, P = 0.0018; 6.86 ng/mL vs 3.78 ng/mL, P = 0.0008, respectively) and correlated positively with modified Rodnan Skin Score in total SSc patients (r = 0.376, P = 0.0009; r = 0.236, P = 0.018, respectively). In conclusion, an increased serum level of resistin associated with increased endothelin-1 and fractalkine level and decreased adiponectin level may indicate a significant role of the adipose tissue in the development and progression of vascular abnormalities in patients with systemic sclerosis. Fractalkine and galectin-3 may participate in promoting and exacerbating the fibrotic process in SSc.

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Section: Discussionmentioning

confidence: 99%

Altered serum level of metabolic and endothelial factors in patients with systemic sclerosis

et al. 2019

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“…However, pulmonary hypertension (PH) has a complex pathophysiology, and it is a progressive disease characterized by angioproliferative vasculopathy in the pulmonary arterioles leading to increased pulmonary vascular resistance and subsequent pulmonary arterial pressure. 3 Due to its complex pathophysiology, there should be more explanations for regression of pulmonary arterial pressure beyond the volume depletion by hemodialysis.…”

Section: The Complexity Of Pulmonary Hypertensionmentioning

confidence: 99%

“…Pulmonary hypertension consists of a group of diseases with a resting mean pulmonary artery pressure ≥25 mmHg measured during right heart catheterization. 3,4 Furthermore, changes in pulmonary vasculature seem to be irreversible in many conditions, irrespective of underlying mechanism. 5 Hence, prevention of volume overload should not be the main reason of regression of pulmonary arterial pressure, in particular, in the presence of treatment with drugs affecting pulmonary vasculature.…”

Section: The Complexity Of Pulmonary Hypertensionmentioning

confidence: 99%

The complexity of pulmonary hypertension

Eyuboglu¹

2019

Hemodialysis International

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“…Its main clinical features are increased pulmonary vascular resistance and pulmonary artery pressure, which ultimately leads to right heart failure and even death. [1][2][3] The pathophysiological mechanism of PAH is very complicated, and pulmonary vascular remodeling is the main pathological change in PAH. The influencing factors of pulmonary vascular remodeling involve a variety of cells, importantly, the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is the most important cause of pulmonary vascular remodeling in PAH.…”

Section: Introductionmentioning

confidence: 99%

<p>eIF2α promotes vascular remodeling via autophagy in monocrotaline-induced pulmonary arterial hypertension rats</p>

Guo

Tian

et al. 2019

DDDT

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These authors contributed equally to this workPurpose: Eukaryotic initiation factor 2α (eIF2α) plays important roles in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in animal hypoxia-induced pulmonary hypertension models. However, the underlying mechanism remains unknown at large. Autophagy has been reported to play a key role in the vascular remodeling in pulmonary arterial hypertension (PAH). The purposes of this study are to determine the functions of eIF2α and autophagy in the vascular remodeling of the monocrotaline-induced PAH rats and to clarify the correlation between eIF2α and autophagy. Methods: We established a rat model of monocrotaline-induced PAH, and we established a cell model of platelet derived growth factor (PDGF)-induced PASMCs proliferation. The vascular morphology and the expression of eIF2α, LC3B, and p62 were assessed in the pulmonary arterial tissue of Sprague-Dawleyrats and PDGF-induced PASMCs. Results: Autophagy was significantly active in monocrotaline model group (MCT)-induced PAH rats, which obviously promotes vascular remodeling in MCT-induced PAH rats. Furthermore, the proliferation of PASMCs was induced by PDGF in vitro. The expression of LC3B, eIF2α was increased in the PDGF-induced PASMCs proliferation, and the expression of p62 was reduced in the PDGF-induced PASMCs proliferation. Moreover, eIF2α siRNA downregulated the expression of eIF2α and LC3B, and upregulated the expression of p62 in PDGF-induced PASMCs proliferation. eIF2α siRNA inhibited the PDGF-induced PASMCs proliferation. Finally, chloroquine can upregulate the protein expression of LC3B and p62, it also can inhibit proliferation in PDGF-induced PASMCs. Conclusion: Based on these observations, we conclude that eIF2α promotes the proliferation of PASMCs and vascular remodeling in monocrotaline-induced PAH rats through accelerating autophagy pathway.

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Pulmonary Arterial Hypertension: Pathophysiology and Treatment

Cited by 103 publications

References 102 publications

Altered serum level of metabolic and endothelial factors in patients with systemic sclerosis

Altered serum level of metabolic and endothelial factors in patients with systemic sclerosis

The complexity of pulmonary hypertension

<p>eIF2α promotes vascular remodeling via autophagy in monocrotaline-induced pulmonary arterial hypertension rats</p>

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