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Circulation Research Apr 2022There is an increased appreciation for the importance of the right heart and pulmonary circulation in several disease states across the spectrum of pulmonary... (Review)
Review
There is an increased appreciation for the importance of the right heart and pulmonary circulation in several disease states across the spectrum of pulmonary hypertension and left heart failure. However, assessment of the structure and function of the right heart and pulmonary circulation can be challenging, due to the complex geometry of the right ventricle, comorbid pulmonary airways and parenchymal disease, and the overlap of hemodynamic abnormalities with left heart failure. Several new and evolving imaging modalities interrogate the right heart and pulmonary circulation with greater diagnostic precision. Echocardiographic approaches such as speckle-tracking and 3-dimensional imaging provide detailed assessments of regional systolic and diastolic function and volumetric assessments. Magnetic resonance approaches can provide high-resolution views of cardiac structure/function, tissue characterization, and perfusion through the pulmonary vasculature. Molecular imaging with positron emission tomography allows an assessment of specific pathobiologically relevant targets in the right heart and pulmonary circulation. Machine learning analysis of high-resolution computed tomographic lung scans permits quantitative morphometry of the lung circulation without intravenous contrast. Inhaled magnetic resonance imaging probes, such as hyperpolarized 129Xe magnetic resonance imaging, report on pulmonary gas exchange and pulmonary capillary hemodynamics. These approaches provide important information on right ventricular structure and function along with perfusion through the pulmonary circulation. At this time, the majority of these developing technologies have yet to be clinically validated, with few studies demonstrating the utility of these imaging biomarkers for diagnosis or monitoring disease. These technologies hold promise for earlier diagnosis and noninvasive monitoring of right heart failure and pulmonary hypertension that will aid in preclinical studies, enhance patient selection and provide surrogate end points in clinical trials, and ultimately improve bedside care.
Topics: Heart Failure; Humans; Hypertension, Pulmonary; Pulmonary Circulation; Xenon Isotopes
PubMed: 35482838
DOI: 10.1161/CIRCRESAHA.121.319990 -
Biomolecules Sep 2021A variety of cell types in pulmonary arteries (endothelial cells, fibroblasts, and smooth muscle cells) are continuously exposed to mechanical stimulations such as shear... (Review)
Review
A variety of cell types in pulmonary arteries (endothelial cells, fibroblasts, and smooth muscle cells) are continuously exposed to mechanical stimulations such as shear stress and pulsatile blood pressure, which are altered under conditions of pulmonary hypertension (PH). Most functions of such vascular cells (e.g., contraction, migration, proliferation, production of extracellular matrix proteins, etc.) depend on a key event, i.e., the increase in intracellular calcium concentration ([Ca]) which results from an influx of extracellular Ca and/or a release of intracellular stored Ca. Calcium entry from the extracellular space is a major step in the elevation of [Ca], involving a variety of plasmalemmal Ca channels including the superfamily of stretch-activated channels (SAC). A common characteristic of SAC is that their gating depends on membrane stretch. In general, SAC are non-selective Ca-permeable cation channels, including proteins of the TRP (Transient Receptor Potential) and Piezo channel superfamily. As membrane mechano-transducers, SAC convert physical forces into biological signals and hence into a cell response. Consequently, SAC play a major role in pulmonary arterial calcium homeostasis and, thus, appear as potential novel drug targets for a better management of PH.
Topics: Animals; Biomechanical Phenomena; Biophysical Phenomena; Calcium Channels; Humans; Hypertension, Pulmonary; Models, Biological; Pulmonary Circulation
PubMed: 34572602
DOI: 10.3390/biom11091389 -
Pulmonary Circulation 2021Pulmonary arterial hypertension is a rare disease of the pulmonary vasculature, characterised pathologically by proliferation, remodelling and thrombosis .... (Review)
Review
Pulmonary arterial hypertension is a rare disease of the pulmonary vasculature, characterised pathologically by proliferation, remodelling and thrombosis . Unfortunately, existing therapeutic interventions do not reverse these findings and the disease continues to result in significant morbidity and premature mortality. A number of haematological derangements have been described in pulmonary arterial hypertension which may provide insights into the pathobiology of the disease and opportunities to explore new therapeutic pathways. These include quantitative and qualitative platelet abnormalities, such as thrombocytopaenia, increased mean platelet volume and altered platelet bioenergetics. Furthermore, a hypercoagulable state and aberrant negative regulatory pathways can be observed, which could contribute to thrombosis in situ in distal pulmonary arteries and arterioles. Finally, there is increasing interest in the role of extracellular vesicle autocrine and paracrine signalling in pulmonary arterial hypertension, and their potential utility as biomarkers and novel therapeutic targets. This review focuses on the potential role of platelets, extracellular vesicles and coagulation pathways in the pathobiology of pulmonary arterial hypertension. We highlight important unanswered clinical questions and the implications of these observations for future research and pulmonary arterial hypertension-directed therapies.
PubMed: 34158919
DOI: 10.1177/20458940211021036 -
Antioxidants & Redox Signaling Oct 2019Redox homeostasis is finely tuned and governed by distinct intracellular mechanisms. The dysregulation of this either by external or internal events is a fundamental... (Review)
Review
Redox homeostasis is finely tuned and governed by distinct intracellular mechanisms. The dysregulation of this either by external or internal events is a fundamental pathophysiologic base for many pulmonary diseases. Based on recent discoveries, it is increasingly clear that cellular redox state and oxidation of signaling molecules are critical modulators of lung disease and represent a final common pathway that leads to poor respiratory outcomes. Based on the wide variety of stimuli that alter specific redox signaling pathways, improved understanding of the disease and patient-specific alterations are needed for the development of therapeutic targets. For the full comprehension of redox signaling in pulmonary disease, it is essential to recognize the role of reactive oxygen intermediates in modulating biological responses. This review summarizes current knowledge of redox signaling in pulmonary development and pulmonary vascular disease.
Topics: Animals; Humans; Lung; Oxidation-Reduction; Signal Transduction; Sulfhydryl Compounds; Vascular Remodeling
PubMed: 30648397
DOI: 10.1089/ars.2018.7712 -
Frontiers in Pediatrics 2022Pulmonary hypertension associated with congenital heart disease (CHD-PH) encompasses different conditions confounded by the left-to-right shunt, left heart obstruction,... (Review)
Review
Pulmonary hypertension associated with congenital heart disease (CHD-PH) encompasses different conditions confounded by the left-to-right shunt, left heart obstruction, ventricular dysfunction, hypoxia due to airway obstruction, dysplasia/hypoplasia of the pulmonary vasculature, pulmonary vascular obstructive disease, and genetic variations of vasoactive mediators. Pulmonary input impedance consists of the pulmonary vascular resistance (Rp) and capacitance (Cp). Rp is calculated as the transpulmonary pressure divided by the pulmonary cardiac output, whereas Cp is calculated as the pulmonary stroke volume divided by the pulmonary arterial pulse pressure. The plots of Rp and Cp demonstrate a unique hyperbolic relationship, namely, the resistor-capacitor coupling curve, which represents the pulmonary vascular condition. The product of Rp and Cp is the exponential pressure decay, which refers to the time constant. Alterations in Cp are more considerable in CHD patients at an early stage of developing pulmonary hypertension or with excessive pulmonary blood flow due to a left-to-right shunt. The importance of Cp has gained attention because recent reports have shown that low Cp potentially reflects poor prognosis in patients with CHD-PH and idiopathic pulmonary hypertension. It is also known that Cp levels decrease in specific populations, such as preterm infants and trisomy 21. Therefore, both Rp and Cp should be individually evaluated in the management of children with CHD-PH who have different disease conditions.
PubMed: 36313863
DOI: 10.3389/fped.2022.1011631 -
International Journal of Molecular... Jun 2023Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive... (Review)
Review
Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive backward transmission of elevated left heart pressures in the setting of heart failure, either with preserved (HFpEF) or reduced (HFrEF) ejection fraction, which increases the pulsatile afterload of the right ventricle (RV) by reducing pulmonary artery (PA) compliance. In a subset of patients, progressive remodeling of the pulmonary circulation resulted in a pre-capillary phenotype of PH, with elevated pulmonary vascular resistance (PVR) further increasing the RV afterload, eventually leading to RV-PA uncoupling and RV failure. The primary therapeutic objective in PH-LHD is to reduce left-sided pressures through the appropriate use of diuretics and guideline-directed medical therapies for heart failure. When pulmonary vascular remodeling is established, targeted therapies aiming to reduce PVR are theoretically appealing. So far, such targeted therapies have mostly failed to show significant positive effects in patients with PH-LHD, in contrast to their proven efficacy in other forms of pre-capillary PH. Whether such therapies may benefit some specific subgroups of patients (HFrEF, HFpEF) with specific hemodynamic phenotypes (post- or pre-capillary PH) and various degrees of RV dysfunction still needs to be addressed.
Topics: Humans; Hypertension, Pulmonary; Heart Failure; Stroke Volume; Pulmonary Circulation; Hemodynamics
PubMed: 37373119
DOI: 10.3390/ijms24129971 -
Internal Medicine (Tokyo, Japan) Feb 2023
Topics: Humans; Hypertension, Pulmonary; Pulmonary Circulation; Thromboembolism; Pulmonary Embolism; Chronic Disease
PubMed: 35793955
DOI: 10.2169/internalmedicine.0017-22 -
The Journal of Thoracic and... Oct 2021
Topics: Fontan Procedure; Humans; Pulmonary Circulation; Pyrimidines; Sulfonamides
PubMed: 33451847
DOI: 10.1016/j.jtcvs.2020.11.121 -
BioMed Research International 2022Vascular remodeling refers to changes in the size, contraction, distribution, and flow rate of blood vessels and even changes in vascular function. Vascular remodeling... (Review)
Review
Vascular remodeling refers to changes in the size, contraction, distribution, and flow rate of blood vessels and even changes in vascular function. Vascular remodeling can cause cardiovascular and cerebrovascular diseases. It can also lead to other systemic diseases, such as pulmonary hypertension, pulmonary atherosclerosis, chronic obstructive pulmonary disease, stroke, and ascites of broilers. Hypoxia is one of the main causes of vascular remodeling. Prolonged hypoxia or intermittent hypoxia can lead to loss of lung ventilation, causing respiratory depression, irregular respiratory rhythms, and central respiratory failure. Animals that are unable to adapt to the highland environment are also prone to sustained constriction of the small pulmonary arteries, increased resistance to pulmonary circulation, and impaired blood circulation, leading to pulmonary hypertension and right heart failure if they live in a highland environment for long periods of time. However, limited studies have been found on the relationship between hypoxia and vascular remodeling. Therefore, this review will explore the relationship between hypoxia and vascular remodeling from the aspects of endoplasmic reticulum stress, mitochondrial dysfunction, abnormal calcium channel, disordered cellular metabolism, abnormal expression of miRNA, and other factors. This will help to understand the detailed mechanism of hypoxia-mediated smooth muscle cell proliferation and vascular remodeling for the better treatment and management of diseases due to vascular remodeling.
Topics: Animals; Vascular Remodeling; Chickens; Hypertension, Pulmonary; Hypoxia; Cell Proliferation; Muscle, Smooth; Myocytes, Smooth Muscle; Pulmonary Artery
PubMed: 36593773
DOI: 10.1155/2022/3959845 -
The Journal of Thoracic and... Oct 2021
Topics: Fontan Procedure; Hemodynamics; Homeostasis; Humans; Models, Cardiovascular; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Pulmonary Circulation; Treatment Outcome; Univentricular Heart; Vascular Resistance
PubMed: 33618865
DOI: 10.1016/j.jtcvs.2020.08.114