Follistatin lowers blood pressure and improves vascular structure and function in essential and secondary hypertension.

Hypertension is characterized by resistance artery remodeling driven by oxidative stress and fibrosis. We previously showed that an activin A antagonist, follistatin, inhibited renal oxidative stress and fibrosis in a model of hypertensive chronic kidney disease. Here, we investigate the effects of follistatin on blood pressure and vascular structure and function in models of essential and secondary hypertension.

Inhibitory Antibodies against PCSK9 Reduce Surface CD36 and Mitigate Diet-Induced Renal Lipotoxicity.

Background: PCSK9 modulates the uptake of circulating lipids through a range of receptors, including the low-density lipoprotein receptor (LDLR) and CD36. In the kidney, CD36 is known to contribute to renal injury through pro-inflammatory and -fibrotic pathways. In this study, we sought to investigate the role of PCSK9 in modulating renal lipid accumulation and injury through CD36 using a high fat diet (HFD)-induced murine model.

Inhibition of histone deacetylation with vorinostat does not prevent tunicamycin-mediated acute kidney injury.

Endoplasmic reticulum (ER) stress is associated with acute kidney injury (AKI) caused by various mechanisms, including antibiotics, non-steroidal anti-inflammatory drugs, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic that induces ER stress and is a commonly used model of AKI. 4-phenylbutyrate (4-PBA) is a chemical chaperone and histone deacetylase (HDAC) inhibitor and has been shown to protect the kidney from ER stress, apoptosis, and structural damage in a tunicamycin model of AKI.

TDAG51 induces renal interstitial fibrosis through modulation of TGF-β receptor 1 in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by the gradual loss of renal function and is a major public health concern. Risk factors for CKD include hypertension and proteinuria, both of which are associated with endoplasmic reticulum (ER) stress. ER stress-induced TDAG51 protein expression is increased at an early time point in mice with CKD.

Enhanced Myogenic Constriction in the SHR Preglomerular Vessels Is Mediated by Thromboxane A2 Synthesis.

Background: Spontaneously Hypertensive Rats (SHR) have chronically elevated blood pressures at 30 weeks of age (systolic: 191.0 ± 1.0, diastolic: 128.

Protein misfolding in endoplasmic reticulum stress with applications to renal diseases.

Protein misfolding may be the result of a variety of different processes that disrupt the ability of a protein to form a thermodynamically stable tertiary structure that allows it to perform its proper function. In this chapter, we explore the nature of a protein's form that allows it to have a stable tertiary structure, and examine specific mutation that are known to occur in the coding regions of DNA that disrupt a protein's ability to be folded into a thermodynamically stable tertiary structure. We examine the consequences of these protein misfoldings in terms of the endoplasmic reticulum stress response and resulting unfolded protein response.

Surfactant specific ionic strength effects on membrane fouling during produced water treatment.

Membrane filtration is a technique that can be successfully applied to remove oil from stable oil-in-water emulsions. This is especially interesting for the re-use of produced water (PW), a water stream stemming from the petrochemical industry, which contains dispersed oil, surface-active components and often has a high ionic strength. Due to the complexity of this emulsion, membrane fouling by produced water is more severe and less understood than membrane fouling by more simple oil-in-water emulsions.

Endoplasmic reticulum stress inhibition blunts the development of essential hypertension in the spontaneously hypertensive rat.

Essential hypertension is the leading cause of premature death worldwide. However, hypertension's cause remains uncertain. endoplasmic reticulum (ER) stress has recently been associated with hypertension, but it is unclear whether ER stress causes hypertension.

Adhesion of emulsified oil droplets to hydrophilic and hydrophobic surfaces - effect of surfactant charge, surfactant concentration and ionic strength.

Adhesion of emulsified oil droplets to a surface plays an important role in processes such as crossflow membrane filtration, where the oil causes fouling. We present a novel technique, in which we study oil droplets on a model surface in a flow cell under shear force to determine the adhesive force between droplets and surface. We prepared an emulsion of hexadecane and used hydrophilic and hydrophobic glass slides as model surfaces.

Produced water treatment by membranes: A review from a colloidal perspective.

While the world faces an increased scarcity in fresh water supply, it is of great importance that water from industry and waste streams can be treated for re-use. One of the largest waste streams in the oil and gas industry is produced water. After the phase separation of oil and gas, the produced water is left.

Analysis of the potency of various low molecular weight chemical chaperones to prevent protein aggregation.

Newly translated proteins must undergo proper folding to ensure their function. To enter a low energy state, misfolded proteins form aggregates, which are associated with many degenerative diseases, such as Huntington's disease and chronic kidney disease (CKD). Recent studies have shown the use of low molecular weight chemical chaperones to be an effective method of reducing protein aggregation in various cell types.

Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria.

Endoplasmic reticulum (ER) stress is implicated in chronic kidney disease (CKD) development in patients and in animal models. Here we show that ER stress inhibition through 4-phenylbutyric acid (4-PBA) administration decreases blood pressure, albuminuria, and tubular casts in an angiotensin II/deoxycorticosterone acetate/salt murine model of CKD. Lower albuminuria in 4-PBA-treated mice was associated with higher levels of cubilin protein in renal tissue membrane fractions.

Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl salt-sensitive rat.

Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment.

Alterations to the middle cerebral artery of the hypertensive-arthritic rat model potentiates intracerebral hemorrhage.

Aims: We have recently created an age-dependent hypertensive-mono-arthritic animal model from the stroke-resistant spontaneously hypertensive rat to model populations with autoimmune disease who are hypertensive and are prone to stroke. The model exhibits signs of hemorrhagic stroke (HS) subsequent to chronic inflammation and hypertension. HS is also associated with the inability of middle cerebral arteries to undergo pressure dependent constriction (PDC).

Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance.

Essential hypertension is a complex multifactorial disease process that involves the interaction of multiple genes at various loci throughout the genome, and the influence of environmental factors such as diet and lifestyle, to ultimately determine long-term arterial pressure. These factors converge with physiological signaling pathways to regulate the set-point of long-term blood pressure. In hypertension, structural changes in arteries occur and show differences within and between vascular beds, between species, models and sexes.

GRP78 and CHOP modulate macrophage apoptosis and the development of bleomycin-induced pulmonary fibrosis.

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated the role of GRP78, the main UPR regulator, in an experimental model of lung injury and fibrosis. Grp78(+/-) , Chop(-/-) and wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation and lungs were examined at days 7 and 21.

Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function.

Objective: Our purpose was to determine if endoplasmic reticulum stress inhibition lowers blood pressure (BP) in hypertension by correcting vascular dysfunction.

Methods: The spontaneously hypertensive rat (SHR) was used as a model of human essential hypertension with its normotensive control, the Wistar Kyoto rat. Animals were subjected to endoplasmic reticulum stress inhibition with 4-phenylbutyric acid (4-PBA; 1 g/kg per day, orally) for 5 weeks from 12 weeks of age.

Major comorbid disease processes associated with increased incidence of acute kidney injury.

Acute kidney injury (AKI) is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment.

Acute kidney injury: preclinical innovations, challenges, and opportunities for translation.

Background: Acute kidney injury (AKI) is a clinically important condition that has attracted a great deal of interest from the biomedical research community. However, acute kidney injury AKI research findings have yet to be translated into significant changes in clinical practice.

Objective: This article reviews many of the preclinical innovations in acute kidney injury AKI treatment, and explores challenges and opportunities to translate these finding into clinical practice.

Development of a Model of Chronic Kidney Disease in the C57BL/6 Mouse with Properties of Progressive Human CKD.

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression.

Crosstalk between the unfolded protein response and NF-κB-mediated inflammation in the progression of chronic kidney disease.

The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression.

The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis.

Recently, there has been an increasing amount of literature published on the effects of 4-phenylbutyric acid (4-PBA) in various biological systems. 4-PBA is currently used clinically to treat urea cycle disorders under the trade name Buphenyl. Recent studies however have explored 4-PBA in the context of a low weight molecular weight chemical chaperone.