scholarly journals Pulmonary hypertension: Proteins in the blood

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Martin Wilkins
Keyword(s):  
Pulmonary Hypertension ◽  
New Technology ◽  
Local Environment ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Plasma Proteome ◽  
Bioinformatic Tools ◽  
Non Invasive ◽  
New Biomarkers ◽  
Small Aliquot

The plasma proteome is rich in information. It comprises proteins that are secreted or lost from cells as they respond to their local environment. Changes in the constitution of the plasma proteome offer a relatively non-invasive report on the health of tissues. This is particularly true of the lung in pulmonary hypertension, given the large surface area of the pulmonary vasculature in direct communication with blood. So far, this is relatively untapped; we have relied on proteins released from the heart, specifically brain natriuretic peptide and troponin, to inform clinical management. New technology allows the measurement of a larger number of proteins that cover a broad range of molecular pathways in a single small aliquot. The emerging data will yield more than just new biomarkers of pulmonary hypertension for clinical use. Integrated with genomics and with the help of new bioinformatic tools, the plasma proteome can provide insight into the causative drivers of pulmonary vascular disease and guide drug development.

4971Blood viscosity and its relevance to the diagnosis and management of pulmonary hypertension: a new elephant in the cathlab

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kempny ◽  
K Dimopoulos ◽  
A E Fraisse ◽  
G P Diller ◽  
L C Price ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Catheterization ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Significant Difference ◽  
The Difference ◽  
Clinically Significant ◽  
The Relationship

Abstract Background Pulmonary vascular resistance (PVR) is an essential parameter assessed during cardiac catheterization. It is used to confirm pulmonary vascular disease, to assess response to targeted pulmonary hypertension (PH) therapy and to determine the possibility of surgery, such as closure of intra-cardiac shunt or transplantation. While PVR is believed to mainly reflect the properties of the pulmonary vasculature, it is also related to blood viscosity (BV). Objectives We aimed to assess the relationship between measured (mPVR) and viscosity-corrected PVR (cPVR) and its impact on clinical decision-making. Methods We assessed consecutive PH patients undergoing cardiac catheterization. BV was assessed using the Hutton method. Results We included 465 patients (56.6% female, median age 63y). The difference between mPVR and cPVR was highest in patients with abnormal Hb levels (anemic patients: 5.6 [3.4–8.0] vs 7.8Wood Units (WU) [5.1–11.9], P<0.001; patients with raised Hb: 10.8 [6.9–15.4] vs. 7.6WU [4.6–10.8], P<0.001, respectively). Overall, 33.3% patients had a clinically significant (>2.0WU) difference between mPVR and cPVR, and this was more pronounced in those with anemia (52.9%) or raised Hb (77.6%). In patients in the upper quartile for this difference, mPVR and cPVR differed by 4.0WU [3.4–5.2]. Adjustment of PVR required Conclusions We report, herewith, a clinically significant difference between mPVR and cPVR in a third of contemporary patients assessed for PH. This difference is most pronounced in patients with anemia, in whom mPVR significantly underestimates PVR, whereas in most patients with raised Hb, mPVR overestimates it. Our data suggest that routine adjustment for BV is necessary.

Pulmonary Hypertension Due to Valvular Heart Disease: Aortic and Mitral

2015 ◽  
Vol 14 (2) ◽  
pp. 95-101
Author(s):  
Ryan Karl Kaple ◽  
Evelyn M. Horn
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Aortic Valve ◽  
Valvular Heart Disease ◽  
Treatment Options ◽  
Venous Hypertension ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Surgical Interventions ◽  
Valve Lesions

Pulmonary hypertension (PH) can be due to a primary pulmonary vasculature abnormality, but is more often secondary to lung, cardiac, or environmental insults, and is frequently multifactorial. Most commonly, left heart disease is at fault, a subset of which is valvular heart disease (VHD). With sufficient time, most chronic left-sided valve lesions will result in some element of PH. Long-standing PH causes pulmonary vascular remodeling and progressive PH due to reduced vascular compliance. Careful monitoring of VHD progression is critical, both through screening imaging and patient education, in order to properly time intervention to prevent the development or worsening of PH. The primary diagnostic tool in PH due to VHD is echocardiography, while invasive hemodynamic evaluation can be helpful to determine PH etiology or severity when echocardiography is not adequate. The presence of PH in VHD is often an indication for intervention, but it also increases procedural risk. Severe PH, however, has not been proven to preclude safe intervention, but rather should prompt full preprocedural evaluation and close intra- and postprocedural monitoring. Valve replacement or repair can be viewed as a treatment for PH secondary to the valvular lesion. Percutaneous alternatives to surgical interventions are available for some mitral and aortic valve conditions. Though in relatively early stages of development, these less invasive procedures may improve the safety profile of valve interventions. Pulmonary hypertension that fails to improve after intervention should raise suspicion for procedural failure or underlying pulmonary vascular disease (either precapillary possibly in association with interstitial lung disease or scleroderma or secondary to combined pre-/postcapillary PH due to long-standing pulmonary venous hypertension). This review is focused on the pathophysiology, treatment options, and outcomes in patients with PH due to mitral and aortic valve lesions.

A review of exercise pulmonary hypertension in systemic sclerosis

2019 ◽  
Vol 4 (3) ◽  
pp. 225-237
Author(s):  
Faisal Shaikh ◽  
Zafia Anklesaria ◽  
Tasneam Shagroni ◽  
Rajeev Saggar ◽  
Luna Gargani ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Vascular Disease ◽  
Underlying Mechanism ◽  
Pulmonary Vascular Disease ◽  
Non Invasive ◽  
History Of ◽  
Prognostic Implications ◽  
Definition Of ◽  
The Right

In general, pulmonary vascular disease has important negative prognostic implications, regardless of the associated condition or underlying mechanism. In this regard, systemic sclerosis is of particular interest as it is the most common connective tissue disease associated with pulmonary hypertension, and a well-recognized at-risk population. In the setting of systemic sclerosis and unexplained dyspnea, the concept of using exercise to probe for underlying pulmonary vascular disease has acquired significant interest. In theory, a diagnosis of systemic sclerosis–associated exercise pulmonary hypertension may allow for earlier therapeutic intervention and a favorable alteration in the natural history of the pulmonary vascular disease. In the context of underlying systemic sclerosis, the purpose of this article is to provide a comprehensive review of the evolving definition of exercise pulmonary hypertension, the current role and methodologies for non-invasive and invasive exercise testing, and the importance of the right ventricle.

scholarly journals The role of RNA m6A methylation in the regulation of postnatal hypoxia-induced pulmonary hypertension

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shanshan Xu ◽  
Xuefeng Xu ◽  
Ziming Zhang ◽  
Lingling Yan ◽  
Liyan Zhang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Development ◽  
Weight Ratio ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Postnatal Exposure ◽  
Sprague Dawley ◽  
Adult Rats ◽  
The Impact

Abstract Background Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that (1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and (2) m6A modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH. Methods Twenty-four male Sprague–Dawley rats were exposed to a hypoxic environment (FiO2: 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular pressure (RVP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze m6A modification changes in lung tissue in 2- and 9-week-old rats that were exposed to postnatal hypoxia. Results Mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. m6A methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct m6A modification peak-related genes differed between the two groups, and these genes were associated with lung development. Conclusions Our results indicate postnatal hypoxia can cause PH, which can persist into adulthood. The development and persistence of PH may be because of the continuous low expression of methyltransferase like 3 affecting the m6A level of PH-related genes. Our findings provide new insights into the impact of postnatal hypoxia and the role of m6A in the development of pulmonary vascular pathophysiology.

scholarly journals The pathophysiology of chronic thromboembolic pulmonary hypertension

2017 ◽  
Vol 26 (143) ◽  
pp. 160112 ◽  
Author(s):  
Gérald Simonneau ◽  
Adam Torbicki ◽  
Peter Dorfmüller ◽  
Nick Kim
Keyword(s):  
Pulmonary Hypertension ◽  
Small Vessel Disease ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Small Vessel ◽  
Treatment Modalities ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Substantial Impact ◽  
Vessel Disease ◽  
Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres.

Chronic thromboembolic pulmonary hypertension

ESC CardioMed ◽  
2018 ◽  
pp. 2550-2554
Author(s):  
Yu Taniguchi ◽  
Xavier Jaïs ◽  
Gérald Simonneau ◽  
Marc Humbert
Keyword(s):  
Pulmonary Hypertension ◽  
Small Vessel Disease ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Flow Distribution ◽  
Small Vessel ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Vessel Disease ◽  
Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and progressive pulmonary vascular disease that is usually the consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organized thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis, and underlying haematological or autoimmune disorders, including splenectomy and antiphospholipid antibodies. Small pulmonary vessel remodelling also contributes to haemodynamic compromise, functional impairment, and disease progression in CTEPH. Small vessel disease can occur in non-obstructed areas as well as downstream from occlusions (possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries). The degree of small vessel disease has a substantial impact on the severity of CTEPH and post-surgical outcomes. Surgical, interventional, and medical treatment of CTEPH aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle, and prevent or treat small vessel disease.

scholarly journals An official European Respiratory Society statement: pulmonary haemodynamics during exercise

2017 ◽  
Vol 50 (5) ◽  
pp. 1700578 ◽  
Author(s):  
Gabor Kovacs ◽  
Philippe Herve ◽  
Joan Albert Barbera ◽  
Ari Chaouat ◽  
Denis Chemla ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Scientific Evidence ◽  
Cardiopulmonary Exercise Testing ◽  
Clinical Importance ◽  
Pulmonary Vascular Disease ◽  
European Respiratory Society ◽  
Gold Standard Method ◽  
Non Invasive ◽  
Right Heart Catheterisation ◽  
Pulmonary Haemodynamics

There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term “exercise pulmonary hypertension” may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions. Exercise pulmonary hypertension is associated with the presence of a modest elevation of resting mean PAP and requires clinical follow-up, particularly if risk factors for pulmonary hypertension are present. There is a lack of robust clinical evidence on targeted medical therapy for exercise pulmonary hypertension.

Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats

1991 ◽  
Vol 70 (2) ◽  
pp. 561-566 ◽  
Author(s):  
Y. L. Lai ◽  
J. W. Olson ◽  
M. N. Gillespie
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Wall Thickness ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Functional Study ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Alveolar Wall ◽  
Lung Dysfunction

Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post-MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post-MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities.

scholarly journals Revisiting a Distinct Entity in Pulmonary Vascular Disease: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 355
Author(s):  
Munish Sharma ◽  
Deborah Jo Levine
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Progressive Increase ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Pulmonary Thromboendarterectomy ◽  
Percutaneous Balloon ◽  
Definitive Therapy ◽  
Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a specific type of pulmonary hypertension (PH) and the major component of Group 4 pulmonary hypertension (PH). It is caused by pulmonary vasculature obstruction that leads to a progressive increase in pulmonary vascular resistance and, ultimately, to failure of the right ventricle. Pulmonary thromboendarterectomy (PEA) is the only definitive therapy, so a timely diagnosis and early referral to a specialized PEA center to determine candidacy is prudent for a favorable outcome. Percutaneous balloon pulmonary angioplasty (BPA) has a potential role in patients unsuitable for PEA. Medical therapy with riociguat is the only PH-specific medical therapy currently approved for the treatment of inoperable or persistent CTEPH. This review article aims to revisit CTEPH succinctly with a review of prevailing literature.

scholarly journals The Role of RNA m6A Methylation in the Regulation of Postnatal Hypoxia-induced Pulmonary Hypertension

2020 ◽  
Author(s):  
shanshan xu ◽  
Xuefeng Xu ◽  
Ziming Zhang ◽  
Lingling Yan ◽  
Liyan Zhang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Development ◽  
Systolic Pressure ◽  
Weight Ratio ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Adult Rats ◽  
The Impact

Abstract Background: Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that 1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and 2) m6A modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH.Methods: Forty male Sprague-Dawley rats were exposed to a hypoxic environment (FiO2: 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular systolic pressure (RVSP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze m6A modification changes in lung tissue between 2 and 9 weeks following exposure to postnatal hypoxia.Results: mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. m6A methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct m6A modification peak-related genes differed between the two groups, and these genes were associated with lung development.Conclusions: Our results indicate postnatal hypoxia dysregulates lung development, leading to PH, and may have a long-term effect on adult rat lung development via the alterations in pulmonary vasculature function. METTL3, a m6A methyltransferase, was elevated in rats exposed to postnatal hypoxia in both the postnatal period and in adulthood, suggesting that it contributes to the development of PH following postnatal hypoxia. Our findings provide new insights into the impact of postnatal hypoxia and the role of m6A in the development of pulmonary vascular pathophysiology.

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