Osteopontin and Galectin-3 As Biomarkers of Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension

Keranov, Stanislav; Dörr, Oliver; Jafari, Leili; Liebetrau, Christoph; Keller, Till; Troidl, Christian; Riehm, Jessica; Rutsatz, Wiebke; Bauer, Pascal; Voss, Sandra; Richter, Manuel J.; Tello, Khodr; Gall, Henning; Ghofrani, Hossein Ardeschir; Guth, Stefan; Seeger, Werner; Hamm, Christian W.; Nef, Holger

doi:10.2217/bmm-2021-0009

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…Osteopontin, which our LC–MS/MS analysis identified at higher levels in CDH, is highly expressed by pulmonary artery smooth muscle cells and adventitial fibroblasts from patients with pulmonary hypertension 30 , 31 and osteopontin levels in serum correlate with pulmonary hypertension severity 32 , 33 , prompting us to select it for further evaluation. The random forest model suggested that osteopontin was the second most influential variable in predicting CDH, although it did not reach statistical significance, which may change with a larger sample size.…”

Section: Discussionmentioning

confidence: 92%

“…However, there is no prior suggestion of an association with CDH or pulmonary hypertension. Galectin-3 was reported as a biomarker in pulmonary hypertension and associated right ventricular dysfunction and has been shown to stimulate the proliferation of smooth muscle cells in vitro 32 , 37 – 39 . It was reported to be elevated in amniotic fluid following cytomegalovirus infection 40 , but an association with CDH was not previously reported.…”

Section: Discussionmentioning

confidence: 99%

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Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid

Bhutada,

Tran-Lundmark,

Kramer

et al. 2023

Sci Rep

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Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and treatment response. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37–39 weeks) from women with normal pregnancies (n = 5) or carrying fetuses with CDH (n = 5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, in the MSP–RON signaling in macrophages pathway and in networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Differences in selected proteins, namely pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin-3 were validated by orthogonal testing using ELISA in larger cohorts and showed statistically significant differences aiding in the diagnosis and prediction of CDH. The findings provide potential tools for clinical management of CDH.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid

Bhutada,

Tran-Lundmark,

Kramer

et al. 2023

Sci Rep

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show abstract

“…Macrophages are key regulators of fibrogenesis through their interactions with myofibroblasts, wound healing responses, and production of profibrotic factors like galectin-3, osteopontin, and transforming growth factor- beta (TGF-β) ( 71 – 74 ). We and others have previously shown that CD163+ and CD206+ cardiac macrophage accumulation and monocyte activation correlates with cardiac inflammation and fibrosis with HIV and SIV infection ( 38 , 75 – 77 ).…”

Section: Conclusion- Discussionmentioning

confidence: 99%

Simian immunodeficiency virus-infected rhesus macaques with AIDS co-develop cardiovascular pathology and encephalitis

White,

Walker,

Wang

et al. 2023

Front. Immunol.

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Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently than SIVE or CVD pathology alone. Their co-development correlated more strongly with activated myeloid cells, increased numbers of CD14+CD16+ monocytes, plasma CD163 and interleukin-18 (IL-18) than did SIVE or CVD pathology alone, or no pathology. Animals with both SIVE and CVD pathology had greater numbers of cardiac macrophages and increased collagen and monocyte/macrophage accumulation, which were better correlates of CVD-pathology than SIV-RNA. Animals with SIVE alone had higher levels of activated macrophage biomarkers and cardiac macrophage accumulation than SIVnoE animals. These observations were confirmed in HIV infected individuals with HIV encephalitis (HIVE) that had greater numbers of cardiac macrophages and fibrosis than HIV-infected controls without HIVE. These results underscore the notion that CNS and CVD pathologies frequently occur together in HIV and SIV infection, and demonstrate an unmet need for adjunctive therapies targeting macrophages.

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“…Thus, Gal-3 can prematurely identify the onset of right ventricle remodeling in patients with PAH and is positively associated with the right ventricular systolic and diastolic indices [ 85 ]. On the other hand, Gal-3 was not able to differentiate between adaptive and maladaptive RV remodeling in PAH patients within the study of Keranov et al [ 86 ].…”

Section: Gal-3 In Congenital Heart Diseasementioning

confidence: 99%

The Role of Galectin-3 in Predicting Congenital Heart Disease Outcome: A Review of the Literature

Făgărășan

Săsăran

Gozar

et al. 2023

IJMS

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Galectin-3 (Gal-3) is a novel pro-fibrotic biomarker that can predict both right and left cardiac dysfunction caused by various cardiovascular conditions. Its expression seems to be progressively altered with evolving cardiac remodeling processes, even before the onset of heart failure. Hence, Gal-3 has been found to be an individual predictor of acute and chronic heart failure or to serve as part of an integrated biomarker panel that can foresee adverse cardiac outcomes. In congenital heart disease (CHD), Gal-3 correlates with cardiac mortality and complications in both children and adults and is proposed as a therapeutic target in order to reverse the activation of pro-fibrosis pathways that lead to heart failure. Positive associations between serum Gal-3 levels, post-operatory hospitalization rates, complications and ventricular dysfunction have also been reported within studies conducted on patients with CHD who underwent corrective surgery. Thus, this review tried to address the potential utility of Gal-3 in patients with CHD and particularly in those who undergo corrective surgery. The heterogeneity of the literature data and the lack of validation of the results obtained by the current studies on larger cohorts cannot be neglected, though. Further longitudinal research is required to establish how Gal-3 can relate to long-term outcomes in pediatric CHD.

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Osteopontin and Galectin-3 As Biomarkers of Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension

Cited by 6 publications

References 30 publications

Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid

Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid

Simian immunodeficiency virus-infected rhesus macaques with AIDS co-develop cardiovascular pathology and encephalitis

The Role of Galectin-3 in Predicting Congenital Heart Disease Outcome: A Review of the Literature

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