Effect of Plasma Protein Depletion on BNP-32 Recovery

Hawkridge, Adam M.; Muddiman, David C.; Hebulein, Denise M.; Cataliotti, Alessandro; Burnett, John C.

doi:10.1373/clinchem.2007.098038

Cited by 11 publications

(7 citation statements)

References 5 publications

(6 reference statements)

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“…Studies indicate that in subjects with cardiovascular diseases the biological structure of these hormones may be altered, thus reducing their protective activities [6, 7]. Furthermore, recent studies have established that basal blood pressure and risk for HTN are linked to common genetic variants of the ANP ( NPPA ) and BNP ( NPPB ) genes [8].…”

Section: Introductionmentioning

confidence: 99%

Cardiac BNP gene delivery prolongs survival in aged spontaneously hypertensive rats with overt hypertensive heart disease

Tonne

Holditch

Oehler

et al. 2014

Aging

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BackgroundHypertension is a highly prevalent disease associated with cardiovascular morbidity and mortality. Recent studies suggest that patients with hypertension also have a deficiency of certain cardiac peptides. Previously we demonstrated that a single intravenous injection of the myocardium-tropic adeno-associated virus (AAV) 9-based vector encoding for proBNP prevented the development of hypertensive heart disease (HHD) in spontaneously hypertensive rats (SHRs). The current study was designed to determine the duration of cardiac transduction after a single AAV9 injection and to determine whether cardiac BNP overexpression can delay the progression of previously established HHD, and improve survival in aged SHRs with overt HHD.Methods and ResultsTo evaluate the duration of cardiac transduction induced by the AAV9 vector, we used four week old SHRs. Effective long-term selective cardiac transduction was determined by luciferase expression. A single intravenous administration of a luciferase-expressing AAV9 vector resulted in efficient cardiac gene delivery for up to 18-months. In aged SHRs (9-months of age), echocardiographic studies demonstrated progression of HHD in untreated controls, while AAV9-BNP vector treatment arrested the deterioration of cardiac function at six months post-injection (15-months of age). Aged SHRs with established overt HHD were further monitored to investigate survival. A single intravenous injection of the AAV9-vector encoding rat proBNP was associated with significantly prolonged survival in the treated SHRs (613±38 days, up to 669 days) compared to the untreated rats (480±69 days, up to 545 days)(p<0.05).ConclusionsA single intravenous injection of AAV9 vector elicited prolonged cardiac transduction (up to 18 months post-injection). AAV9 induced cardiac BNP overexpression prevented development of congestive heart failure, and significantly prolonged the survival of aged SHRs with previously established overt HHD. These findings support the beneficial effects of chronic supplementation of BNP in a frequent and highly morbid condition such as HHD.

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Section: Introductionmentioning

confidence: 99%

Cardiac BNP gene delivery prolongs survival in aged spontaneously hypertensive rats with overt hypertensive heart disease

Tonne

Holditch

Oehler

et al. 2014

Aging

Self Cite

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“…A potential alternative to pre-fractionation is abundant protein depletion to reduce the overall protein complexity and dynamic range of plasma [23] and thus limit the ion suppression resulting from abundant glycans derived from the most abundant glycoproteins. Protein depletion has been used to reduce complexity and selectively enhance a number of proteomic experiments [24–27]. In addition, it is possible that few or all of these glycans are solely derived from the different glycoforms of the abundant proteins in plasma.…”

Section: Introductionmentioning

confidence: 99%

The effects of abundant plasma protein depletion on global glycan profiling using NanoLC FT-ICR mass spectrometry

Bereman

Muddiman

2010

Anal Bioanal Chem

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We report the results of abundant plasma protein depletion on the analysis of underivatized N-linked glycans derived from plasma proteins by nanoLC Fourier-transform ion cyclotron resonance mass spectrometry. N-linked glycan profiles were compared between plasma samples where the six most abundant plasma proteins were depleted (n=3) through a solid-phase immunoaffinity column and undepleted plasma samples (n=3). Three exogenous glycan standards were spiked into all samples which allowed for normalization of the N-glycan abundances. The abundances of 20 glycans varying in type, structure, composition, and molecular weight (1,200–3,700 Da) were compared between the two sets of samples. Small fucosylated non-sialylated complex glycans were found to decrease in abundance in the depleted samples (greater than or equal to tenfold) relative to the undepleted samples. Protein depletion was found to marginally effect (less than threefold) the abundance of high mannose, hybrid, and large highly sialylated complex species. The significance of these findings in terms of future biomarker discovery experiments via global glycan profiling is discussed.

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“…The natriuretic paradox is that although patients present in the clinic with high BNP measurements they often do not experience a natriuretic benefit. As a result, high scrutiny has been placed upon the assays used for BNP measurements [82,83]. The superior selectivity and multiplexing capabilities inherent to LC-MS allows for the differentiation of specific BNP molecules that are active on the NPRA receptor (and have natriuretic benefit) such as BNP1-32 along with other degradation fragments that are not considered active.…”

Section: Lc-ms In Measurements Of Pharmacodynamic Proteinsmentioning

confidence: 99%