Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

Lagos-Carvajal, A.; Neto, Francisco José Teixeira; Becerra-Velásquez, Diana Rocío; Diniz, Miriely Steim; Klein, Adriana Vieira; Rocha, Thalita; Dias‐Junior, Carlos A.

doi:10.1016/j.lfs.2015.08.013

Cited by 4 publications

(4 citation statements)

References 29 publications

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“… 3 Moreover, acute pulmonary embolism (APE) can also lead to PAH following the obstruction of the pulmonary vascular vessels. 4 Proliferation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) induces vascular lumen obstruction in the late stage. 5 Despite the progress made in recent years regarding the treatment of PAH, these options have limited efficacy in treating the disease.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1β and IL-6

Ou¹,

Zhang²,

Chen³

et al. 2020

Molecular Therapy - Nucleic Acids

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Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease that could eventually result in right ventricular failure. Recently, the roles of microRNAs (miRNAs) in PAH have been highlighted. The present study aims to investigate the effects of miRNA (miR)-340-5p on PAH induced by acute pulmonary embolism (APE) and the underlying mechanisms. miR-340-5p was lowly expressed, whereas interleukin 1β (IL-1β) and IL-6 were highly expressed in plasma of APE-PAH patients as compared to normal human plasma. Subsequently, IL-1β and IL-6 were confirmed to be two target genes of miR-340-5p using a dual-luciferase reporter gene assay. By conducting overexpression and rescue experiments, overexpression of miR-340-5p was evidenced to inhibit proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and inflammation via reducing IL-1β and IL-6 levels. Meanwhile, miR-340-5p led to the blocked nuclear factor κB (NF-κB) pathway with reduced NF-κB p65, matrix metalloproteinase 2 (MMP2), and MMP9 expression in PASMCs. Finally, the ameliorative effect of miR-340-5p on pathological lesions was further verified in rat models of APE-PAH. Altogether, overexpressed miR-340-5p inhibited the inflammatory response, proliferation, and migration of PASMCs by downregulating IL-1β and IL-6, thereby suppressing the progression of APE-PAH. miR-340-5p therefore holds promise as an anti-inflammatory therapeutic target.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1β and IL-6

Ou¹,

Zhang²,

Chen³

et al. 2020

Molecular Therapy - Nucleic Acids

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“…We evaluated the area of MPA bifurcation by linking the three center points among MPA bifurcation on the centerline. The elevated right ventricular overload caused by PH was the main cause of poor short-term prognosis (Lagos-Carvajal et al, 2015). This increasing overload can cause the location center point on the MPA outlet plane to shift toward the MPA inlet plane (Schievano et al, 2011), and the location of The AUCs in the training set were 0.860 (95% CI: 0.795-0.912) and 0.621 (95% CI: 0.538-0.699).…”

Section: Discussionmentioning

confidence: 99%

“…However, the parameters are numerous and miscellaneous. The elevated right ventricular overload caused by pulmonary hypertension (PH) is the main cause of poor short-term prognosis (Lagos-Carvajal et al, 2015). Mechanical obstruction, the release of inflammatory factors and reflex hypoxemia are all involved in the pathophysiology of acute PE (Aviram et al, 2016;Jia et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

A Novel Predictive Method Incorporating Parameters of Main Pulmonary Artery Bifurcation for Short-Term Prognosis in Non-high-risk Acute Pulmonary Embolism Patients

Dong

Hou

et al. 2020

Front. Physiol.

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The aim of this study was to build a formula to predict short-term prognosis using main pulmonary artery (MPA) parameters reconstructed from computed tomographic pulmonary angiography in non-high-risk acute pulmonary embolism (PE) patients. After reconstructing the MPA and its centerline, the MPA, the right and left pulmonary artery inlet, and the MPA outlet plane were differentiated to measure the cross-sectional area (CSA), the maximal diameter and the hydraulic diameter. The MPA bifurcation area, volume and angle were measured. MPA dilation was defined as >29 mm at the transverse section plane. The patients were randomly divided into a training set and a validation set. A least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used to build a predictive formula. The performances of the predictive formula from LASSO were tested by the area under the receiver operating characteristic curve (AUC) and precision-recall (PR) curve with 10-fold cross-validation. The clinical utility was assessed by decision curve analysis (DCA). In total, 296 patients were enrolled and randomly divided (50:50) into a training set and a validation set. The LASSO predictive formula (lambda.1SE) was as follows: 0.92 × MPA bifurcation area + 0.50 × MPA outlet hydraulic diameter + 0.10 × MPA outlet CSA. The AUCs of the predictive formula were 0.860 (95% CI: 0.795-0.912) and 0.943 (95% CI: 0.892-0.975) in the training set and validation set, respectively. The LASSO predictive formula had a higher average area under the PR curve than MPA dilation (0.71 vs. 0.23 in the training set and 0.55 vs. 0.23 in the validation set) and added a net benefit in clinical utility by DCA. Integration of MPA outlet CSA, hydraulic diameter, and bifurcation area with the LASSO predictive formula as a novel weighting method facilitated the prediction of poor short-term prognosis within 30 days after hospital admission in non-high-risk acute PE patients.

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“…Models of exogenous PE inject pre-formed thrombus material into the pulmonary circulation. The majority are based on artificial thrombus material such as glass beads or plastic spheres (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(50)(51)(52). While nonphysiological, these models create a predictable increase in PVR and RV strain.…”

Section: Artificial Exogenous Pe Modelsmentioning

confidence: 99%

Animal models of right heart failure

Andersen¹,

Feen²,

Andersen³

et al. 2020

Cardiovasc Diagn Ther

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Right heart failure may be the ultimate cause of death in patients with acute or chronic pulmonary hypertension (PH). As PH is often secondary to other cardiovascular diseases, the treatment goal is to target the underlying disease. We do however know, that right heart failure is an independent risk factor, and therefore, treatments that improve right heart function may improve morbidity and mortality in patients with PH. There are no therapies that directly target and support the failing right heart and translation from therapies that improve left heart failure have been unsuccessful, with the exception of mineralocorticoid receptor antagonists. To understand the underlying pathophysiology of right heart failure and to aid in the development of new treatments we need solid animal models that mimic the pathophysiology of human disease. There are several available animal models of acute and chronic PH. They range from flow induced to pressure overload induced right heart failure and have been introduced in both small and large animals.When initiating new pre-clinical or basic research studies it is key to choose the right animal model to ensure successful translation to the clinical setting. Selecting the right animal model for the right study is hence important, but may be difficult due to the plethora of different models and local availability. In this review we provide an overview of the available animal models of acute and chronic right heart failure and discuss the strengths and limitations of the different models.

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Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

Cited by 4 publications

References 29 publications

RETRACTED: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1β and IL-6

RETRACTED: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1β and IL-6

A Novel Predictive Method Incorporating Parameters of Main Pulmonary Artery Bifurcation for Short-Term Prognosis in Non-high-risk Acute Pulmonary Embolism Patients

Animal models of right heart failure

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