Pulmonary Hypertension: A Brief Guide for Clinicians

Mandras, Stacy A.; Mehta, Hirsch; Vaidya, Anjali

doi:10.1016/j.mayocp.2020.04.039

Cited by 190 publications

(156 citation statements)

References 33 publications

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“…Clinical subgroups of pulmonary arterial hypertension (PAH), PH due to chronic lung disease or hypoxia, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanism belong to pre-capillary PH. PH due to left-sided heart disease, such as heart failure, belongs to post-capillary PH [ 57 , 58 ]. Vascular remodeling, distensibility, and neural and humoral factors contribute to the development of PH [ 56 , 57 ], in addition to hypoxic, genetic and environmental factors [ 59 ].…”

Section: Ca 2+ Sensitization In Hypertensionmentioning

confidence: 99%

Characterization of Contractile Machinery of Vascular Smooth Muscles in Hypertension

Yang

Hori

2021

Life

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Hypertension is a key risk factor for cardiovascular disease and it is a growing public health problem worldwide. The pathophysiological mechanisms of vascular smooth muscle (VSM) contraction contribute to the development of hypertension. Calcium (Ca2+)-dependent and -independent signaling mechanisms regulate the balance of the myosin light chain kinase and myosin light chain phosphatase to induce myosin phosphorylation, which activates VSM contraction to control blood pressure (BP). Here, we discuss the mechanism of the contractile machinery in VSM, especially RhoA/Rho kinase and PKC/CPI-17 of Ca2+ sensitization pathway in hypertension. The two signaling pathways affect BP in physiological and pathophysiological conditions and are highlighted in pulmonary, pregnancy, and salt-sensitive hypertension.

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Section: Ca 2+ Sensitization In Hypertensionmentioning

confidence: 99%

Characterization of Contractile Machinery of Vascular Smooth Muscles in Hypertension

Yang

Hori

2021

Life

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“…Pulmonary hypertension (PH) shows the symptom of high blood pressure in the lung arteries which impedes the delivery of blood from the heart to the lungs (Mandras et al, 2020). PH is diagnosed by at least 20 mmHg (millimeter of mercury) of the rest-state mean pulmonary arterial pressure (mPAP) and the right-sided heart catheterization (Simonneau et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…PH is diagnosed by at least 20 mmHg (millimeter of mercury) of the rest-state mean pulmonary arterial pressure (mPAP) and the right-sided heart catheterization (Simonneau et al, 2019). Although PH may be caused by various factors, the PH patients painfully suffer from shortness of breath and increased mortality (Mandras et al, 2020). As many as, 10% of people over age 65 are affected by PH, and more than half of them develop heart failure (Hoeper et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

EnRank: An Ensemble Method to Detect Pulmonary Hypertension Biomarkers Based on Feature Selection and Machine Learning Models

Liu¹,

Fu²,

Zhang³

et al. 2021

Front. Genet.

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Pulmonary hypertension (PH) is a common disease that affects the normal functioning of the human pulmonary arteries. The peripheral blood mononuclear cells (PMBCs) served as an ideal source for a minimally invasive disease diagnosis. This study hypothesized that the transcriptional fluctuations in the PMBCs exposed to the PH arteries may stably reflect the disease. However, the dimension of a human transcriptome is much higher than the number of samples in all the existing datasets. So, an ensemble feature selection algorithm, EnRank, was proposed to integrate the ranking information of four popular feature selection algorithms, i.e., T-test (Ttest), Chi-squared test (Chi2), ridge regression (Ridge), and Least Absolute Shrinkage and Selection Operator (Lasso). Our results suggested that the EnRank-detected biomarkers provided useful information from these four feature selection algorithms and achieved very good prediction accuracy in predicting the PH patients. Many of the EnRank-detected biomarkers were also supported by the literature.

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“…4) Severe PAH may result in right ventricular hypertrophy, function failure, and, eventually, premature death. 5,6) It is reported by PAH registries that the mortality rates of PAH cases at 1 and 3 years are 7%-32% and 23%-61%, respectively. 5) During the past two decades, therapeutic approaches for PAH have made a pronounced progress, and currently, four types of drugs can be used for the treatment of PAH, including the prostacyclin analogs and receptor agonists, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and cyclic guanosine monophosphate activators.…”

mentioning

confidence: 99%

“…5,6) It is reported by PAH registries that the mortality rates of PAH cases at 1 and 3 years are 7%-32% and 23%-61%, respectively. 5) During the past two decades, therapeutic approaches for PAH have made a pronounced progress, and currently, four types of drugs can be used for the treatment of PAH, including the prostacyclin analogs and receptor agonists, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and cyclic guanosine monophosphate activators. 7,8) Despite the limited beneficial impacts on hemodynamics-related quality of life, disease progression, and survival, the currently available pharmaceutical therapies do not cure PAH, and the median survival rate remains less than 3 years from diagnosis, highlighting the urgent need for extensive researches to reveal the molecular mechanisms underlying PAH.…”

mentioning

confidence: 99%

SOX17 Loss-of-Function Mutation Underlying Familial Pulmonary Arterial Hypertension

Wang

et al. 2021

Int. Heart J.

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Pulmonary arterial hypertension (PAH) refers to a rare, progressive disorder that is characterized by occlusive pulmonary vascular remodeling, resulting in increased pulmonary arterial pressure, right-sided heart failure, and eventual death. Emerging evidence from genetic investigations of pediatric-onset PAH highlights the strong genetic basis underpinning PAH, and deleterious variants in multiple genes have been found to cause PAH. Nevertheless, PAH is of substantial genetic heterogeneity, and the genetic defects underlying PAH in the overwhelming majority of cases remain elusive. In this investigation, a consanguineous family suffering from PAH transmitted as an autosomal-dominant trait was identified. Through whole-exome sequencing and bioinformatic analyses as well as Sanger sequencing analyses of the PAH family, a novel heterozygous SOX17 mutation, NM _022454.4: c.379C>T; p.(Gln127*), was found to co-segregate with the disease in the family, with complete penetrance. The nonsense mutation was neither observed in 612 unrelated healthy volunteers nor retrieved in the population genetic databases encompassing the Genome Aggregation Database, the Exome Aggregation Consortium database, and the Single Nucleotide Polymorphism database. Biological analyses using a dual-luciferase reporter assay system revealed that the Gln127*-mutant SOX17 protein lost the ability to transcriptionally activate its target gene NOTCH1. Moreover, the Gln127*-mutant SOX17 protein exhibited no inhibitory effect on the function of CTNNB1-encode β-catenin, which is a key player in vascular morphogenesis. This research firstly links SOX17 loss-of-function mutation to familial PAH, which provides novel insight into the molecular pathogenesis of PAH, suggesting potential implications for genetic and prognostic risk evaluation as well as personalized prophylaxis of the family members affected with PAH.

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Pulmonary Hypertension: A Brief Guide for Clinicians

Cited by 190 publications

References 33 publications

Characterization of Contractile Machinery of Vascular Smooth Muscles in Hypertension

Characterization of Contractile Machinery of Vascular Smooth Muscles in Hypertension

EnRank: An Ensemble Method to Detect Pulmonary Hypertension Biomarkers Based on Feature Selection and Machine Learning Models

SOX17 Loss-of-Function Mutation Underlying Familial Pulmonary Arterial Hypertension

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