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Schematic illustration of inflammation and infection-mediated vascular remodeling: upon stimulation by infection and/or inflammation, lung vascular cells produce and release inflammatory mediators (chemokines and cytokines), thereby recruiting the inflammatory cells. Under the coordination of inflammatory mediators, inflammatory cells can promote the release of cytokines and chemokines, which leads to chronic vasoconstriction, vascular remodeling by vascular cell proliferation, collagen deposition and plexiform lesions. The progressive process causes pulmonary arterial hypertension.
Source publication
Pulmonary hypertension (PH) comprises five groups of serious clinical entities characterized by pulmonary artery vasoconstriction and vascular remodeling leading to right heart failure and death. In addition to vascular remodeling, recruitment and exaggerated accumulation of several perivascular inflammatory cells is also observed, including macrop...
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Cardiac remodelling is characterized by abnormal changes in the function and morphological properties such as diameter, mass, normal diameter of cavities, heart shape, fibrosis, thickening of vessels and heart layers, cardiomyopathy, infiltration of inflammatory cells, and some others. These damages are associated with damage to systolic and diasto...
Citations
... Some theories suggest that the increased inflammatory response associated with these skin conditions could potentially affect the phases of wound healing, which are inflammation, proliferation, and remodeling (202,203). For instance, an exaggerated inflammatory response might lead to prolonged or chronic inflammation, delaying the progression to the subsequent phases of wound healing (204)(205)(206). Furthermore, if COVID-19 affects the blood vessels in the skin, as has been suggested by the presentation of pseudo-chilblain lesions (206,207), this could impair the delivery of oxygen and nutrients essential for wound healing (208, 209). ...
Neutrophils play a critical role in the immune response to infection and tissue injury. However, recent studies have shown that neutrophils are a heterogeneous population with distinct subtypes that differ in their functional properties. Moreover, aging can alter neutrophil function and exacerbate immune dysregulation. In this review, we discuss the concept of neutrophil heterogeneity and how it may be affected by aging. We then examine the implications of neutrophil heterogeneity and aging for COVID-19 pathogenesis and wound healing. Specifically, we summarize the evidence for neutrophil involvement in COVID-19 and the potential mechanisms underlying neutrophil recruitment and activation in this disease. We also review the literature on the role of neutrophils in the wound healing process and how aging and neutrophil heterogeneity may impact wound healing outcomes. Finally, we discuss the potential for neutrophil-targeted therapies to improve clinical outcomes in COVID-19 and wound healing.
... Specifically, previous reports describe the implication of inteleukin-6 (IL-6) in PH. However, most of them are focused on PH in general terms or only in pulmonary arterial hypertension (PAH) subtype [13,14]. It also well stablished leukocyte-endothelial interaction during the inflammatory process occurs through the interaction of CD44 present on the surface of some leukocytes with glycosaminoglycan hyaluronan, a major component of extracellular matrix [15,16]. ...
... PAH is a common and serious complication of congenital heart disease [24,25]. Although major advances have been made in PAH treatments in recent years, they cannot completely reverse the pathological remodelling and PAH pathogenesis has only been partially elucidated [25]. ...
... PAH is a common and serious complication of congenital heart disease [24,25]. Although major advances have been made in PAH treatments in recent years, they cannot completely reverse the pathological remodelling and PAH pathogenesis has only been partially elucidated [25]. Therefore, a considerable number of genes and pathways related to PAH need to be studied further. ...
Long noncoding RNAs (lncRNAs) are potential regulators of a variety of cardiovascular diseases. Therefore, there is a series of differentially expressed lncRNAs in pulmonary arterial hypertension (PAH) that may be used as markers to diagnose PAH and even predict the prognosis. However, their specific mechanisms remain largely unknown. Therefore, we investigated the biological role of lncRNAs in patients with PAH. First, we screened patients with PAH secondary to ventricular septal defect (VSD) and those with VSD without PAH to assess differences in lncRNA and mRNA expression between the two groups. Our results revealed the significant upregulation of 813 lncRNAs and 527 mRNAs and significant downregulation of 541 lncRNAs and 268 mRNAs in patients with PAH. Then, we identified 10 hub genes in a constructed protein-protein interaction network. Next, we performed bioinformatics analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis and subsequently constructed coding-noncoding co-expression networks. We screened lncRNA-TCONS_00008552 and lncRNA-ENST00000433673 as candidate genes and verified the expression levels of the lncRNAs using quantitative reverse-transcription PCR. Although expression levels of lncRNA-TCONS_00008552 in the plasma from the PAH groups were significantly increased compared with the control groups, there was no significant difference in the expression of lncRNA-ENST00000433673 between the two groups. This study bolsters our understanding of the role of lncRNA in PAH occurrence and development and indicates that lncRNA-TCONS_00008552 is a novel potential molecular marker for PAH.
... Currently, we use a delayed closure of the abdominal defect that could be responsible for significant inflammation around the peritoneal sac linked to local and chronic infection between the skin and the peritoneal sac. Several studies have shown interest in treating inflammation associated with PH [32]. However, further studies are required to evaluate whether inflammation management may improve the prognosis and management of short-and long-term complications. ...
Our objective is to determine perinatal factors contributing to the development of pulmonary hypertension (PH) in patients with isolated giant omphaloceles (GO). All cases of omphaloceles that underwent prenatal and postnatal care at the University Hospital of Lille between 1996 and 2021 were reviewed. We included all infants with isolated GO, including at least a part of the liver, who were treated by delayed surgical closure. Prenatal and postnatal data were recorded and correlated with postnatal morbidities. We compared outcomes between a group of infants with GO who developed PH and infants with GO with no PH. We identified 120 infants with omphalocele. Fifty isolated GO cases fulfilled the inclusion criteria of our study. The incidence of PH was 30%. We highlighted a prolonged inflammatory state, defined as a CRP superior to 15 mg/L, platelets higher than 500 G/L, and white blood cells higher than 15 G/l for more than 14 days in patients who developed PH. This event occurred in 73% of patients with PH versus 21% of patients without PH (p < 0.05). Late-onset infection was not different between the two groups. We speculate that prolonged inflammatory syndrome promotes PH in infants with GO treated with delayed surgical closure.
... The increased cytokine production that we observed at 1-year follow-up in IPAH patients was not present in CTD-PAH patients, suggesting that this increase may be due to disease progression or disease-specific response to therapy, rather than a direct immunomodulatory effect of the PAH specific medication. However, effects of PAH-specific medication cannot be excluded, because these drugs have some immunomodulatory effects [35]. This may also explain the heterogeneity seen within the IPAH and CTD-PAH patient groups, whereby some patients show increased cytokine production capacity and others show decreased cytokine production capacity at follow-up. ...
Pulmonary arterial hypertension (PAH) is rare disease that is categorized as idiopathic (IPAH) when no underlying cause can be identified. Lungs of most patients with IPAH contain increased numbers of T cells and dendritic cells (DCs), suggesting involvement of the immune system in its pathophysiology. However, our knowledge on circulating immune cells in IPAH is rather limited. We used flow cytometry to characterize peripheral blood DCs and T cells in treatment-naive IPAH patients, compared with connective-tissue disease-PAH (CTD-PAH) patients and healthy controls (HCs). At diagnosis, T-helper (Th) cells of IPAH patients were less capable of producing TNFα, IFNγ, IL-4 and IL-17 compared to HCs. IPAH patients showed a decreased frequency of Th2 cells and significantly enhanced expression of the CTLA4 checkpoint molecule in naive CD4+ T cells and both naive and memory CD8+ T cells. Frequencies and surface marker expression of circulating DCs and monocytes were essentially comparable between IPAH patients and HCs. Principal component analysis (PCA) separated IPAH patients—but not CTD-PAH patients—from HCs, based on T-cell cytokine profiles. At 1-year follow-up, the frequencies of IL-17+ production by memory CD4+ T cells were increased in IPAH patients and accompanied by increased proportions of Th17 and Tc17 cells, as well as decreased CTLA4 expression. Treatment-naive IPAH patients displayed a unique T-cell phenotype that was different from CTD-PAH patients and was characterized by reduced cytokine-producing capacity. These findings point to involvement of adaptive immune responses in IPAH, which may have an implication for the development of therapeutic interventions.
People living with HIV (PLWH) face a growing burden of chronic diseases, owing to the combinations of aging, environmental triggers, lifestyle choices, and virus-induced chronic inflammation. The rising incidence of pulmonary vascular diseases represents a major concern for PLWH. The study of HIV-associated pulmonary vascular complications ideally requires a strong understanding of pulmonary vascular cell biology and HIV pathogenesis at the molecular level for effective applications in infectious diseases and vascular medicine. Active HIV infection and/or HIV proteins disturb the delicate balance between vascular tone and constriction, which is pivotal for maintaining pulmonary vascular health. One of the defining features of HIV is its high genetic diversity owing to several factors including its high mutation rate, recombination between viral strains, immune selective pressures, or even geographical factors. The intrinsic HIV genetic diversity has several important implications for pathogenic outcomes of infection and the overall battle to combat HIV. Challenges in the field present themselves from two sides of the same coin: those imposed by the virus itself and those stemming from the host. The field may be advanced by further developing in vivo and in vitro models that are well described for both pulmonary vascular diseases and HIV for mechanistic studies. In essence, the study of HIV-associated pulmonary vascular complications requires a multidisciplinary approach, drawing upon insights from both infectious diseases and vascular medicine. In this review article, we discuss the fundamentals of HIV virology and their impact on pulmonary disease, aiming to enhance the understanding of either area or both simultaneously. Bridging the gap between preclinical research findings and clinical practice is essential for improving patient care. Addressing these knowledge gaps requires interdisciplinary collaborations, innovative research approaches, and dedicated efforts to prioritize HIV-related pulmonary complications on the global research agenda.
Background
The aim of this study is to evaluate the role of leukotriene B4, an inflammatory mediator, in the development of pulmonary hypertension in paediatric patients with CHD with left-right shunt.
Methods
The study included forty patients with CHD with left-right shunts. Based on haemodynamic data obtained from cardiac diagnostic catheterisation, 25 patients who met the criteria for pulmonary arterial hypertension were included in the patient group. The control group comprised 15 patients who did not meet the criteria. The standard cardiac haemodynamic study was conducted. Leukotriene B4 levels were assessed in blood samples taken from both pulmonary arteries and peripheral veins.
Results
The median age of patients with pulmonary arterial hypertension was 10 months (range: 3–168), while the median age of the control group was 50 months (range: 3–194). In the pulmonary hypertension group, the median pulmonary artery systolic/diastolic/mean pressures were 38/18/24 mmHg, compared to 26/10/18 mmHg in the control group. Leukotriene B4 levels in pulmonary artery blood samples were significantly higher in the pulmonary arterial hypertension group compared to the controls (p < 0.05). Peripheral leukotriene B4 levels were also elevated in the pulmonary arterial hypertension group in comparison to the control group, though the difference was not statistically significant.
Conclusion
The discovery of elevated leukotriene B4 levels in pulmonary artery samples from paediatric patients with pulmonary arterial hypertension secondary to CHD with left-to-right shunt suggests that local inflammation may have a pathological role in the development of pulmonary arterial hypertension.
In this study, we hypothesize that angiogenesis of special hepatic vessels such as sinusoid capillaries or veins is closely associated with increasing production of connective tissue in fibrogenesis. Thirty-six male Wistar rats were induced with hepatitis and cirrhosis of the liver using thioacetamide. The number of sinusoidal capillaries, veins, arteries and the area of connective tissue were counted and determined. Immunohistochemical study was performed on paraffin sections using monoclonal mouse anti-CD31. mRNA expression was determined using
qPCR. We found a statistically significant reduction in the number of sinusoidal capillaries (p<0.0001) and an increase in the number of interlobular veins (p<0.0001) in the fibrosis and cirrhosis groups compared to the control group. There are no differences in the number of interlobular arteries (p=0.282) in the three groups. In our analysis, we found that the expression (mRNA) of Fn14 correlated with the number of veins in liver fibrosis (r=0.44, p=0.008). Our data shows that modulation of veins angiogenesis during fibrosis in chronic liver diseases may play an important role in increasing pathological changes of the liver.
Pulmonary hypertension (PH) is a chronic pulmonary vascular disorder characterized by an increase in pulmonary vascular resistance and pulmonary arterial pressure. The detailed molecular mechanisms remain unclear. In recent decades, increasing evidence shows that altered immune microenvironment, comprised of immune cells, mesenchymal cells, extra-cellular matrix and signaling molecules, might induce the development of PH. Myeloid-derived suppressor cells (MDSCs) have been proposed over 30 years, and the functional importance of MDSCs in the immune system is appreciated recently. MDSCs are a heterogeneous group of cells that expand during cancer, chronic inflammation and infection, which have a remarkable ability to suppress T-cell responses and may exacerbate the development of diseases. Thus, targeting MDSCs has become a novel strategy to overcome immune evasion, especially in tumor immunotherapy. Nowadays, severe PH is accepted as a cancer-like disease, and MDSCs are closely related to the development and prognosis of PH. Here, we review the relationship between MDSCs and PH with respect to immune cells, cytokines, chemokines and metabolism, hoping that the key therapeutic targets of MDSCs can be identified in the treatment of PH, especially in severe PH.
