New insights into complement C3 and inflammation in hypertension

Nadar, Sunil; Lip, Gregory Y.H.

doi:10.1038/sj.jhh.1002160

Cited by 15 publications

(13 citation statements)

References 30 publications

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“…Lastly, our survey of C3 and C4 levels demonstrated significantly lower C3 levels associated with BOS 0, and long-term survivors with BOS 0 had the lowest C4 levels of all groups. Although complement levels deplete during acute exacerbations of autoimmune and rheumatological diseases, a broad variety of chronic inflammatory disease states including myocardial inflammation, pancreatic carcinoma, and age-related macular degeneration are associated with higher levels of complement [46-50]. Similarly, our findings suggest that higher complement levels present in higher stages of BOS may coincide with chronic inflammation.…”

Section: Discussionmentioning

confidence: 59%

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

et al. 2012

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BackgroundLong-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS). Mannose binding lectin (MBL) belongs to the innate immune system, participates in complement activation, and may predispose to graft rejection. We investigated mannose binding (MBL) during cold ischemia and in tissue samples from explanted lungs with BOS, and assessed MBL and complement proteins in plasma post-lung transplantation relative to BOS staging.MethodsMBL was detected by immunohistochemistry lung tissue at the time of cold ischemia and in samples with BOS. MBL was assayed in the peripheral blood of 66 lung transplant patients transplanted between 1990–2007.ResultsMBL localized to vasculature and basement membrane during cold ischemia and BOS. Patients further out post-lung transplant > 5 years (n = 33), had significantly lower levels of MBL in the blood compared to lung transplant patients < 5 years with BOS Op-3 (n = 17), 1738 ± 250 ng/ml vs 3198 ± 370 ng/ml, p = 0.027, and similar levels to lung transplant patients < 5 years with BOS 0 (n = 16), 1738 ± 250 ng/ml vs 1808 ± 345 ng/ml. MBL levels in all BOS 0 (n = 30) vs. all BOS Op-3 (n = 36) were 1378 ± 275 ng/ml vs. 2578 ± 390 ng/ml, p = 0.001, respectively. C3 plasma levels in BOS 0 (n = 30) vs. BOS Op-3 (n = 36) were 101 ± 19.8 mg/ml vs. 114 ± 25.2 mg/ml, p = 0.024, respectively.ConclusionsMBL localizes within the lung during graft ischemia and BOS, higher levels of plasma MBL are associated with BOS Op-3 and < 5 years post-transplant, and higher level of plasma complement protein C3 was associated with BOS Op-3 clinical status. MBL may serve as a biomarker for poorer outcome post-lung transplantation.

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Section: Discussionmentioning

confidence: 59%

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

et al. 2012

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“…The level of mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) was decreased in exosomes from the dnA group, while components C3, C4a and C4b were increased in albuminuria condition, pointing to a disfavored lectin pathway. Levels of complement C3 and C4 are also increased in chronic inflammation [ 30 ]. Moreover, excess protein traffic occurs in proteinuric nephropathies, causing an inflammatory response with local increases in C3 [ 31 ], and high baseline levels of C3 correlate with higher risk of developing hypertension, diabetes mellitus or myocardial infarction [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary exosomes reveal protein signatures in hypertensive patients with albuminuria

et al. 2017

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Albuminuria is an indicator of cardiovascular risk and renal damage in hypertensive individuals. Chronic renin–angiotensin system (RAS) suppression facilitates blood pressure control and prevents development of new-onset-albuminuria. A significant number of patients, however, develop albuminuria despite chronic RAS blockade, and the physiopathological mechanisms are underexplored. Urinary exosomes reflect pathological changes taking place in the kidney. The objective of this work was to examine exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression, to find novel clues underlying its development. Patients were followed-up for three years and were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. Exosomal protein alterations between groups were identified by isobaric tag quantitation (iTRAQ). Confirmation was approached by target analysis (SRM). In total, 487 proteins were identified with high confidence. Specifically, 48 proteins showed an altered pattern in response to hypertension and/or albuminuria. Out of them, 21 proteins interact together in three main functional clusters: glycosaminoglycan degradation, coagulation and complement system, and oxidative stress. The identified proteins constitute potential targets for drug development and may help to define therapeutic strategies to evade albuminuria progression in hypertensive patients chronically treated.

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“…Trans-tympanic lactate administration in guinea pigs has been shown to offer significant partial protection against cisplatin-induced ototoxicity, only at a mid-frequency (2 KHz) [56], and when applied by anterosuperior quadrant myringotomies, prior to cisplatin injection resulted in the preservation of the distortion product otoacoustic emissions (DPOAE) [52]. However, another recent study using the intratympanic application of Ringer's lactate solution through a tympanostomy ventilation tube did not provide protection against cisplatin-induced ototoxicity in chinchillas [57]…”

Section: Drugs In Clinical Trialsmentioning

confidence: 99%

The design and screening of drugs to prevent acquired sensorineural hearing loss

Mukherjea

Rybak²,

Sheehan

et al. 2011

Expert Opinion on Drug Discovery

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Introduction-Sensorineural hearing loss affects a high percentage of the population. Ototoxicity is a serious and pervasive problem in patients treated with cisplatin. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed. Similar problems occur with aminoglycoside antibiotic therapy for infections. Noiseinduced hearing loss affects a large number of people. The use of ear protection is not always possible or effective. The prevention of hearing loss with drug therapy would have a huge impact in reducing the number of persons with hearing loss from these major causes.Areas covered-This review discusses significant research findings dealing with the use of protective agents against hearing loss caused by cisplatin, aminoglycoside antibiotics and noise trauma. The efficacy in animal studies and the application of these protective agents in clinical trials that are ongoing are presented.Expert opinion-The reader will gain new insights into current and projected future strategies to prevent sensorineural hearing loss from cisplatin chemotherapy, aminoglycoside antibiotic therapy and noise exposure. The future appears to offer numerous agents to prevent hearing loss caused by cisplatin, aminoglycoside antibiotics and noise. Novel delivery systems will provide ways to guide these protective agents to the desired target areas in the inner ear and will circumvent problems with therapeutic interference of anti-tumor and antibiotics agents and will minimize undesired side effects.

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New insights into complement C3 and inflammation in hypertension

Cited by 15 publications

References 30 publications

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

Urinary exosomes reveal protein signatures in hypertensive patients with albuminuria

The design and screening of drugs to prevent acquired sensorineural hearing loss

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