Cyclooxygenase-2 Expression in Lung in Patients with Congenital Heart Malformations and Pulmonary Arterial Hypertension

Loukanov, Tsvetomir; Jaschinski, Christoph; Kirilov, Milen; Klimpel, Homa; Kretzler, Matthias; Gorenflo, Matthias

doi:10.1055/s-0033-1337446

Cited by 8 publications

(2 citation statements)

References 13 publications

(19 reference statements)

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“…Consistent with previous observations, SC236, a selective COX-2 pharmacological inhibitor, has been found to reduce the production of PGI2 in a rat model of PH and to exacerbate pulmonary artery pressure elevation by increasing sensitivity to endogenous TXA2 while enhancing platelet activation [60]. In addition, studies have reported that COX-2 expression is upregulated in PH caused by congenital heart disease and that COX-2 has a protective effect on blood vessels and inhibits vascular remodeling [61,62]. Inhibition of COX-2 in healthy people and mice has been found to impair renal function while increasing blood pressure and thrombosis [63][64][65].…”

Section: Prostaglandins and Phsupporting

confidence: 85%

The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension

Ye,

Wang,

et al. 2023

Metabolites

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Mild-to-moderate pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). It is characterized by narrowing and thickening of the pulmonary arteries, resulting in increased pulmonary vascular resistance (PVR) and ultimately leading to right ventricular dysfunction. Pulmonary vascular remodeling in COPD is the main reason for the increase of pulmonary artery pressure (PAP). The pathogenesis of PH in COPD is complex and multifactorial, involving chronic inflammation, hypoxia, and oxidative stress. To date, prostacyclin and its analogues are widely used to prevent PH progression in clinical. These drugs have potent anti-proliferative, anti-inflammatory, and stimulating endothelial regeneration properties, bringing therapeutic benefits to the slowing, stabilization, and even some reversal of vascular remodeling. As another well-known and extensively researched prostaglandins, prostaglandin E2 (PGE2) and its downstream signaling have been found to play an important role in various biological processes. Emerging evidence has revealed that PGE2 and its receptors (i.e., EP1–4) are involved in the regulation of pulmonary vascular homeostasis and remodeling. This review focuses on the research progress of the PGE2 signaling pathway in PH and discusses the possibility of treating PH based on the PGE2 signaling pathway.

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Section: Prostaglandins and Phsupporting

confidence: 85%

The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension

Ye,

Wang,

et al. 2023

Metabolites

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“…Mice overexpressing signaling components such as serotonin transporter (SERT), bone morphogenetic protein receptor-2 (BMPR-2), or S100A4 that are involved in right heart failure could only demonstrate details of maladaptive processes in the right heart. More detailed analyses such as investigations in the RV specific ubiquitin-proteasome signaling (83) or analyses of the role of components like cyclooxygenase 2 (84) are needed for gaining deeper insights into right heart diseases. Besides metabolic shifting, ECM remodeling processes are of further interest in research of RV failure in congenital heart defects.…”

Section: Experimental Research With Focus On Rv Dysfunctionmentioning

confidence: 99%

Right Ventricular Failure and Pathobiology in Patients with Congenital Heart Disease – Implications for Long-Term Follow-Up

et al. 2013

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Right ventricular dysfunction represents a common problem in patients with congenital heart defects, such as Tetralogy of Fallot or pulmonary arterial hypertension. Patients with congenital heart defects may present with a pressure or volume overloaded right ventricle (RV) in a bi-ventricular heart or in a single ventricular circulation in which the RV serves as systemic ventricle. Both subsets of patients are at risk of developing right ventricular failure. Obtaining functional and morphological imaging data of the right heart is technically more difficult than imaging of the left ventricle. In contrast to findings on mechanisms of left ventricular dysfunction, very little is known about the pathophysiologic alterations of the right heart. The two main causes of right ventricular dysfunction are pressure and/or volume overload of the RV. Until now, there are no appropriate models available analyzing the effects of pressure and/or volume overload on the RV. This review intends to summarize clinical aspects mainly focusing on the current research in this field. In future, there will be increasing attention to individual care of patients with right heart diseases. Hence, further investigations are essential for understanding the right ventricular pathobiology.

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Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats

Somanna

Wörner

Murthy

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASCCOX-1) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASCCOX-1 or untransduced ASCs. The intratracheal administration of ASCCOX-1 3 × 10(6) cells on day 14 after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured on day 35 after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASCCOX-1 persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASCCOX-1 in the lung. These data emphasize the effectiveness of ASCCOX-1 in the treatment of experimentally induced PH.

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Cyclooxygenase-2 Expression in Lung in Patients with Congenital Heart Malformations and Pulmonary Arterial Hypertension

Abstract: We examined the expression of COX-2 in lung tissue from patients with CHD and PAH. We showed that COX-2 is expressed in diseased lung tissue, indicating a relationship between COX-2 and vascular remodeling in pulmonary arteries in CHD.

Cited by 8 publications

References 13 publications

The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension

The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension

Right Ventricular Failure and Pathobiology in Patients with Congenital Heart Disease – Implications for Long-Term Follow-Up

Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats

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