Richard J Johnson

Publications (270)1476.19 Total impact

• Article: REPLY TO: Serum Uric Acid Still Carries Controversies About Its Role in Endothelial Dysfunction.

  Mehmet Kanbay, Osman Turak, Richard J Johnson
  Journal of Clinical Hypertension 04/2013; 15(4):297. · 1.83 Impact Factor
• Article: Uric acid and chronic kidney disease: which is chasing which?

  Richard J Johnson, Takahiko Nakagawa, Diana Jalal, Laura Gabriela Sánchez-Lozada, Duk-Hee Kang, Eberhard Ritz
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  ABSTRACT: Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has been resurrected as a potential contributory risk factor in the development and progression of CKD. Most studies documented that an elevated serum uric acid level independently predicts the development of CKD. Raising the uric acid level in rats can induce glomerular hypertension and renal disease as noted by the development of arteriolosclerosis, glomerular injury and tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD. While further clinical trials are necessary, uric acid is emerging as a potentially modifiable risk factor for CKD.Gout was considered a cause of CKD in the mid-nineteenth century [1], and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients. In their large series of gouty subjects Talbott and Terplan found that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis, glomerulosclerosis and interstitial fibrosis) [2]. Additional studies showed that during life impaired renal function occurred in half of these subjects [3]. As many of these subjects had urate crystals in their tubules and interstitium, especially in the outer renal medulla, the disease became known as gouty nephropathy. The identity of this condition fell in question as the presence of these crystals may occur in subjects without renal disease; furthermore, the focal location of the crystals could not explain the diffuse renal scarring present. In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se [4]. Indeed, gout was removed from the textbooks as a cause of CKD, and the common association of hyperuricemia with CKD was solely attributed to the retention of serum uric acid that is known to occur as the glomerular filtration rate falls.Renewed interest in uric acid as a cause of CKD occurred when it was realized that invalid assumptions had been made in the arguments to dismiss uric acid as a risk factor for CKD [5]. The greatest assumption was that the mechanism by which uric acid would cause kidney disease would be via the precipitation as crystals in the kidney, similar to the way it causes gout. However, when laboratory animals with CKD were made hyperuricemic, the renal disease progressed rapidly despite an absence of crystals in the kidney [6]. Since this seminal study, there has been a renewed interest in the potential role uric acid may have in both acute and CKD. We briefly review some of the major advances that have occurred in this field in the last 15 years.
  Nephrology Dialysis Transplantation 03/2013; · 3.40 Impact Factor
• Article: What Are the Key Arguments Against Uric Acid as a True Risk Factor for Hypertension?

  Richard J Johnson, Laura G Sánchez-Lozada, Marilda Mazzali, Daniel I Feig, Mehmet Kanbay, Yuri Y Sautin
  Hypertension 03/2013; · 6.21 Impact Factor
• Article: What can asymptomatic hyperuricaemia and systemic inflammation in the absence of gout tell us?

  Shinichiro Inaba, Yuri Sautin, Gabriela E Garcia, Richard J Johnson
  Rheumatology (Oxford, England) 02/2013; · 4.24 Impact Factor
• Article: Uric Acid and the Origins of Hypertension.

  Daniel I Feig, Magdalena Madero, Diana I Jalal, L Gabriela Sanchez-Lozada, Richard J Johnson
  The Journal of pediatrics 02/2013; · 4.02 Impact Factor
• Article: Fructokinase, Fructans, Intestinal Permeability, and Metabolic Syndrome: An Equine Connection?

  Richard J Johnson, Chris Rivard, Miguel A Lanaspa, Silvia Otabachian-Smith, Takuji Ishimoto, Christina Cicerchi, Peter R Cheeke, Bridgett Macintosh, Tanja Hess
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  ABSTRACT: Fructose is a simple sugar present in honey and fruit, but can also exist as a polymer (fructans) in pasture grasses. Mammals are unable to metabolize fructans, but certain gram positive bacteria contain fructanases and can convert fructans to fructose in the gut. Recent studies suggest that fructose generated from bacteria, or directly obtained from the diet, can induce both increased intestinal permeability and features of metabolic syndrome, especially the development of insulin resistance. The development of insulin resistance is driven in part by the metabolism of fructose by fructokinase C in the liver, which results in oxidative stress in the hepatocyte. Similarly, the metabolism of fructose in the small bowel by intestinal fructokinase may lead to increased intestinal permeability and endotoxemia. While speculative, these observations raise the possibility that the mechanism by which fructans induce laminitis could involve intestinal and hepatic fructokinase. Further studies are indicated to determine the role of fructanases, fructose and fructokinase in equine metabolic syndrome and laminitis.
  Journal of Equine Veterinary Science 02/2013; 33(2):120-126. · 0.67 Impact Factor
• Article: IMPAIRED PRESSURE NATRIURESIS RESULTING IN SALT SENSITIVE HYPERTENSION IS CAUSED BY TUBULOINTERSTITIAL IMMUNE CELL INFILTRATION IN THE KIDNEY.

  Martha Franco, Edilia Tapia, Rocio Bautista, Ursino Pacheco, José Santamaría, Yasmir Quiroz, Richard J Johnson, Bernardo Rodriguez-Iturbe
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  ABSTRACT: Immune cell infiltration of the kidney is a constant feature in salt sensitive hypertension (SSHTN). We evaluated the relationship between the renal inflammation and pressure natriuresis in the model of salt-sensitive hypertension that results from transient oral administration of Nω-nitro-L-arginine methyl ester (L-NAME). Pressure natriuresis was determined in Sprague-Dawley rats that received 4 weeks of a high salt (4% NaCl) diet starting one week after stopping L-NAME that was administered alone (SSHTN group, n=17) or in association with mycophenolate mofetil (MMF group, n=15). The administration of MMF in association with L-NAME is known to prevent the subsequent development of SSHTN. Control groups received a high (n=12) and normal (0.4%) salt diet (n=20). Rats with SSHTN had increased expression of inflammatory cytokines and oxidative stress. The severity of hypertension correlated directly (p<0.0001) with the number of tubulointerstitial immune cells and angiotensin II-expressing cells. Pressure natriuresis was studied at renal arterial pressures (RAP) of 90, 110, 130 and 150 mmHg. GFR was similar and stable in all groups and renal blood flow was decreased in the SSHTN group. Significantly decreased natriuresis (p<0.05) was found in the SSHTN group at RAPs of 130 and 150 mmHg and there was an inverse correlation (p<0.01) between the urinary sodium excretion and the number of tubulointerstitial inflammatory cells (lymphocytes and macrophages) and cells expressing angiotensin II. We conclude that tubulointerstitial inflammation plays a key role in the impairment of pressure natriuresis that results in salt dependent hypertension in this experimental model.
  AJP Renal Physiology 01/2013; · 4.42 Impact Factor
• Article: The role of uric acid in the pathogenesis of human cardiovascular disease.

  Mehmet Kanbay, Mark Segal, Baris Afsar, Duk-Hee Kang, Bernardo Rodriguez-Iturbe, Richard J Johnson
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  ABSTRACT: Hyperuricaemia is common in subjects with cardiovascular disease, but is not commonly considered a true risk factor. Recent studies suggest that uric acid is biologically active and can stimulate oxidative stress, endothelial dysfunction, inflammation and vasoconstriction. Epidemiological studies have found that uric acid can independently predict the development of hypertension, as well as stroke and heart failure. Experimentally raising uric acid in animals increases blood pressure, and pilot studies suggest that lowering uric acid in humans can reduce blood pressure in hypertensive individuals. Uric acid may also have emerging roles in the pathogenesis of kidney disease, metabolic syndrome and diabetes. More studies need to be performed on the pathophysiology and clinical consequences of hyperuricaemia in cardiovascular disease.
  Heart (British Cardiac Society) 01/2013; · 4.22 Impact Factor
• Article: SYNERGISTIC EFFECT OF URICASE BLOCKADE PLUS PHYSIOLOGIC AMOUNTS OF FRUCTOSE-GLUCOSE ON GLOMERULAR HYPERTENSION AND OXIDATIVE STRESS IN RATS.

  Edilia Tapia, Magdalena Cristobal, Fernando E Garcia-Arroyo, Virgilia Soto, Fabiola Monroy-Sánchez, Ursino Pacheco, Miguel A Lanaspa, Carlos A Roncal-Jimenez, David Cruz-Robles, Takuji Ishimoto, Magdalena Madero, Richard J Johnson, Laura Gabriela Sanchez-Lozada
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  ABSTRACT: Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n=7/group) were studied during 8 weeks: Water+Vehicle (V), Water+Oxonic acid (OA, 750 mg/k BW), SB (11% fructose-glucose combination)+V and SB+OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension and SB alone induced insulin resistance. SB+OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone, and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic triglycerides, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose.
  AJP Renal Physiology 01/2013; · 4.42 Impact Factor
• Article: Circulating angiopoietin-2 is a marker for early cardiovascular disease in children on chronic dialysis.

  Rukshana C Shroff, Karen L Price, Maria Kolatsi-Joannou, Alexandra F Todd, David Wells, John Deanfield, Richard J Johnson, Lesley Rees, Adrian S Woolf, David A Long
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  ABSTRACT: Cardiovascular disease (CVD) is increasingly recognised as a complication of childhood chronic kidney disease (CKD) even in the absence of diabetes and hypertension. We hypothesized that an alteration in angiopoietin-1 and -2, growth factors which regulate endothelial and vascular function could be involved. We report that the endothelial survival factor, angiopoietin-1 is low in children with pre-dialysis CKD whereas the pro-inflammatory angiopoietin-2 is elevated in children on dialysis. In dialysis patients, angiopoietin-2 positively correlated with time on dialysis, systolic blood pressure, and carotid artery intima media thickness. Elevated angiopoietin-2 levels in dialysis versus pre-dialysis CKD patients were also associated with an anti-angiogenic (high soluble VEGFR-1 and low VEGF-A) and pro-inflammatory (high urate, E-selectin, P-selectin and VCAM-1) milieu. Ang-2 was immunodetected in arterial biopsy samples whilst the expression of VEGF-A was significantly downregulated in dialysis patients. Serum urate correlated with angiopoietin-2 levels in dialysis patients and addition of uric acid was able to induce rapid release of angiopoietin-2 from cultured endothelial cells. Thus, angiopoietin-2 is a marker for cardiovascular disease in children on chronic dialysis and may act as an anti-angiogenic and pro-inflammatory effector in this context. The possibility that the release of angiopoietin-2 from endothelia is mediated by urate should be explored further.
  PLoS ONE 01/2013; 8(2):e56273. · 4.09 Impact Factor
• Article: Serum uric Acid, inflammation, and nondipping circadian pattern in essential hypertension.

  Osman Turak, Fırat Ozcan, Derya Tok, Ahmet Işleyen, Erdoğan Sökmen, Irfan Taşoğlu, Sinan Aydoğdu, Nihat Sen, Kim McFann, Richard J Johnson, Mehmet Kanbay
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  ABSTRACT: Uric acid (UA) is independently associated with the emergence of hypertension. Nocturnal nondipping pattern of hypertension is associated with a greater risk of cardiovascular, renal, and cerebrovascular complications than dippers. The aim of the present study was to evaluate the relationship between the circadian blood pressure rhythm and UA level in patients with newly diagnosed essential hypertension. The study included 112 essential hypertensive patients and 50 healthy controls. The hypertensive patients were divided into two groups according to the results of 24-hour ambulatory blood pressure monitoring, including 60 dippers (35 men, 25 women; mean age, 52.6±15.8 years) and 52 nondippers (29 men, 23 women; mean age, 55.9±13.2 years). Nondippers had significantly higher serum UA levels than the dippers and controls (5.8±0.8, 5.1±0.9 and 4.2±0.9 mg/dL, respectively; P<.001). Serum high-sensitivity C-reactive protein levels were also significantly higher in the nondipper group than the other groups (P<.001) and significantly correlated with serum UA (r=0.358, P<.001). Multivariate logistic regression analysis revealed an independent positive association between serum UA levels and nondipper pattern (odds ratio, 2.28; 95% confidence interval, 1.33-3.94; P=.003). Serum UA is strongly and independently associated with the nondipper circadian pattern in essential hypertension.
  Journal of Clinical Hypertension 01/2013; 15(1):7-13. · 1.83 Impact Factor
• Article: Impact of Genetic Polymorphisms of SLC2A2, SLC2A5, and KHK on Metabolic Phenotypes in Hypertensive Individuals.

  Myphuong T Le, Maximilian T Lobmeyer, Marcus Campbell, Jing Cheng, Zhiying Wang, Stephen T Turner, Arlene B Chapman, Eric Boerwinkle, John G Gums, Yan Gong, Richard J Johnson, Julie A Johnson
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  ABSTRACT: In the past few decades, consumption of added sugars has increased dramatically. Studies have linked high sugar intake with increased risk for a number of diseases. Importantly, fructose, a component of sugar, has been linked with the development of features of metabolic syndrome. This study determined if single nucleotide polymorphisms in genes involved in fructose transport (solute carrier family 2 facilitated glucose transporter, member 2 (SLC2A2) and solute carrier family 2 facilitated glucose/fructose transporter, member 5 (SLC2A5)) and metabolism (ketohexokinase (KHK)) affect inter-individual variability in metabolic phenotypes, such as increased serum uric acid levels. The influence of SLC2A2, SLC2A5, and KHK SNPs on metabolic phenotypes was tested in 237 European Americans and 167 African Americans from the Pharmacogenomic Evaluation and Antihypertensive Responses (PEAR) study. Using baseline untreated fasting data, associations were considered significant if p≤0.005. These SNPs were then evaluated for potential replication (p≤0.05) using data from the Genetic Epidemiology of Responses to Antihypertensives (GERA) studies. SLC2A5 rs5438 was associated with an increase in serum uric acid in European American males. However, we were unable to replicate the association in GERA. The minor allele of SLC2A2 rs8192675 showed an association with lower high-density lipoproteins in European Americans (A/A: 51.0 mg/dL, A/G: 47.0 mg/dL, G/G: 41.5 mg/dL, p = 0.0034) in PEAR. The association between rs8192675 and lower high-density lipoproteins was replicated in the combined European American GERA study samples (A/A: 47.6 mg/dL, A/G: 48.6 mg/dL, G/G: 41.9 mg/dL, p = 0.0315). The association between SLC2A2 rs8192675 and high-density lipoproteins suggests the polymorphism may play a role in influencing high-density lipoproteins and thus metabolic risk of cardiovascular disease.
  PLoS ONE 01/2013; 8(1):e52062. · 4.09 Impact Factor
• Article: Toll-like receptor 3 ligand, polyIC, induces proteinuria and glomerular CD80, and increases urinary CD80 in mice.

  Takuji Ishimoto, Michiko Shimada, Garcia Gabriela, Tomoki Kosugi, Waichi Sato, Pui Y Lee, Miguel A Lanaspa, Christopher Rivard, Shoichi Maruyama, Eduardo H Garin, Richard J Johnson
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  ABSTRACT: Background We have reported that children with biopsy-proven minimal change disease (MCD) express CD80 (also known as B7.1) in their podocytes and excrete high levels of CD80 in their urine during active nephrotic syndrome. We also reported that polyIC, a Toll-like receptor 3 ligand, increases CD80 mRNA and protein expression in cultured human podocytes dose-dependently, with actin re-organization and a reduction in synaptopodin expression.Methods To determine the effect of polyIC in the kidney, we subjected mice to systemic injection of polyIC or phosphate buffered saline.ResultsMice injected with polyIC developed significant proteinuria with increased urinary CD80 excretion. Glomeruli from mice injected with polyIC were normal by light microscopic examination, but showed increased CD80 production in podocytes by immunofluorescence staining. In isolated glomeruli from mice injected with polyIC, expressions of CD80 and interleukin 10 significantly increased with a mild non-significant increase in CTLA-4, and synaptopodin expression decreased significantly.Conclusions Our study demonstrates that systemically administered polyIC can induce transient proteinuria and urinary CD80 excretion with an increase in CD80 production in podocytes, increased glomerular CD80 and reduced synaptopodin expression. These findings may be relevant to the pathogenesis of proteinuria in MCD.
  Nephrology Dialysis Transplantation 12/2012; · 3.40 Impact Factor
• Article: Uric Acid-Induced Endothelial Dysfunction Is Associated with Mitochondrial Alterations and Decreased Intracellular ATP Concentrations.

  Laura Gabriela Sánchez-Lozada, Miguel A Lanaspa, Magdalena Cristóbal-García, Fernando García-Arroyo, Virgilia Soto, David Cruz-Robles, Takahiko Nakagawa, Min A Yu, Duk-Hee Kang, Richard J Johnson
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  ABSTRACT: Background/Aims: Endothelial dysfunction is associated with mitochondrial alterations. We hypothesized that uric acid (UA), which can induce endothelial dysfunction in vitro and in vivo, might also alter mitochondrial function. Methods: Human aortic endothelial cells were exposed to soluble UA and measurements of oxidative stress, nitric oxide, mitochondrial density, ATP production, aconitase-2 and enoyl Co-A hydratase-1 expressions, and aconitase-2 activity in isolated mitochondria were determined. The effect of hyperuricemia induced by uricase inhibition in rats on renal mitochondrial integrity was also assessed. Results: UA-induced endothelial dysfunction was associated with reduced mitochondrial mass and ATP production. UA also decreased aconitase-2 activity and lowered enoyl CoA hydratase-1 expression. Hyperuricemic rats showed increased mitDNA damage in association with higher levels of intrarenal UA and oxidative stress. Conclusions: UA-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP. These studies provide additional evidence for a deleterious effect of UA on vascular function that could be important in the pathogenesis of hypertension and vascular disease.
  Nephron Experimental Nephrology 12/2012; 121(3-4):e71-e78. · 1.86 Impact Factor
• Article: Sack and sugar, and the aetiology of gout in England between 1650 and 1900.

  Christopher Rivard, Jeffrey Thomas, Miguel A Lanaspa, Richard J Johnson
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  ABSTRACT: A marked increase in gout was observed in England during the 17th to 20th centuries. Many have ascribed this rapid increase in gout to the introduction of wines that were laced with lead. In this article, we suggest another likely contributor, which is the marked increase in sugar intake that occurred in England during this period. Sugar contains fructose, which raises uric acid and increases the risk for gout. Sugar intake increased markedly during this period due to its introduction in liquors, tea, coffee and desserts. We suggest that the introduction of sugar explains why gout was originally a disease of the wealthy and educated, but gradually became common throughout society.
  Rheumatology (Oxford, England) 11/2012; · 4.24 Impact Factor
• Article: Impaired pressure natriuresis is associated with interstitial inflammation in salt-sensitive hypertension.

  Bernardo Rodriguez-Iturbe, Martha Franco, Richard J Johnson
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  ABSTRACT: PURPOSE OF REVIEW: Impairment of the pressure natriuresis relationship is a central event in the pathogenesis of hypertension. Renal tubulointerstitial inflammation results in salt-sensitive hypertension and, until recently, the changes in pressure natriuresis induced by renal inflammation received little attention. RECENT FINDINGS: Oxidative stress and increased intrarenal angiotensin II activity, in association with rarefaction and loss of peritubular vascular network, may be involved in the inflammation-induced blunting of the natriuresis resulting from increments in renal perfusion pressure. SUMMARY: Here, we review the mechanisms for the impairment in pressure natriuresis resulting from renal tubulointerstitial inflammation in reference to the normal physiologic mechanisms involved in this response.
  Current opinion in nephrology and hypertension 11/2012; · 3.96 Impact Factor
• Article: IMMUNE REACTIVITY TO HEAT SHOCK PROTEIN 70 EXPRESSED IN THE KIDNEY IS CAUSE OF SALT SENSITIVE HYPERTENSION.

  Hector Pons, Atilio Ferrebuz, Yasmir Quiroz, Freddy Romero-Vasquez, Gustavo Parra, Richard J Johnson, Bernardo Rodriguez-Iturbe
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  ABSTRACT: Hypertension affects one-third of the adult population of the world. The causes of hypertension are incompletely understood but relative impairment of sodium excretion is central its pathogenesis. Immune cell infiltration in the kidney is a constant finding in hypertension that in association with local angiotensin and oxidants causes a defect in sodium excretion. However, it is unclear if the T cell influx into the kidney responds to nonspecific chemokine cues or is due to antigen-driven immune attraction. We found that T cells in experimentally-induced salt-driven hypertension present a CD4 clonal response to heat shock protein 70 (HSP70) that is overexpressed in the kidney. We used a highly preserved amino acid sequence within the HSP molecule to induce immune tolerance associated with the generation of IL-10 producing regulatory T cells. Immune tolerant rats to HSP70 developed minimal renal inflammation and were preotected from the development of salt-sensitive hypertension. Adoptive transfer of T lymphocytes isolated from spleen of tolerized rats also reversed hypertension. HSP70 gene delivery to the renal vein of the kidneys of rats sensitized to HSP70 caused an increment in blood pressure in response to a high salt diet. The HSP70 peptide used in this work induces a strong proliferative response in peripheral blood lymphocytes of patients with essential hypertension. These studies provide evidence that autoimmunity plays a role in salt-sensitive hypertension and identifies HSP70 expressed in the kidney as one key antigen. These findings raise the possibility of novel approaches to the treatment of this condition.
  AJP Renal Physiology 10/2012; · 4.42 Impact Factor
• Article: Uric acid induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress: Potential Role in Fructose-Dependent and-Independent Fatty Liver.

  Miguel A Lanaspa, Laura G Sanchez-Lozada, Yea-Jin Choi, Christina Cicerchi, Mehmet Kanbay, Carlos A Roncal-Jimenez, Takuji Ishimoto, Nanxing Li, George Marek, Murat Duranay, George Schreiner, Bernardo Rodriguez-Iturbe, Takahiko Nakagawa, Duk-Hee Kang, Yuri Y Sautin, Richard J Johnson
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  ABSTRACT: Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and currently affects one third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that it is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine-degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.
  Journal of Biological Chemistry 10/2012; · 4.77 Impact Factor
• Article: The role of T cells in the pathogenesis of primary hypertension.

  Yasmir Quiroz, Richard J Johnson, Bernardo Rodríguez-Iturbe
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  ABSTRACT: Accumulating evidence indicates that T cells play an important role in the pathogenesis of hypertension. Here we review the investigations that have shown that T cells are infiltrating the kidney in hypertension. Interstitial accumulation of immune cells is associated with increments in oxidative stress and renal angiotensin II activity that result in the impairment in pressure natriuresis. The severity of salt-sensitive hypertension is directly correlated with the intensity of immune cell infiltration in the kidney. Reducing the renal infiltration of T cells prevents or ameliorates hypertension and the induction of tubulointerstitial inflammation results in salt-sensitive hypertension. The potential participation of autoimmune mechanisms in the renal infiltration of immune competent cells is discussed.
  Nephrology Dialysis Transplantation 10/2012; · 3.40 Impact Factor
• Article: Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States: Liver ultrasound data from the National Health and Nutrition Examination Survey.

  Jeffrey C Sirota, Kim McFann, Giovanni Targher, Richard J Johnson, Michel Chonchol, Diana I Jalal
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  ABSTRACT: OBJECTIVE: Experimental and observational studies suggest a role for uric acid in non-alcoholic fatty liver disease (NAFLD). We examined the association between serum uric acid levels and NAFLD in a large population-based study from the United States. MATERIALS/METHODS: A cross-sectional analysis of 10,732 nondiabetic adults who participated in the National Health and Nutrition Examination Survey 1988-1994. Sex specific uric acid quartiles were defined: ≤5.2, 5.3-6.0, 6.1-6.9, and >6.9mg/dL for men and ≤3.7, 3.8-4.5, 4.6-5.3, and >5.3mg/dL for women. NAFLD presence and severity were defined by ultrasonographic detection of steatosis in the absence of other liver diseases. We modeled the probability that more severe NAFLD would be associated with the highest quartiles of uric acid. RESULTS: Compared to the 1st quartile, the odds ratio for NAFLD was 1.79 (95% C.I. 1.49-2.15, p<0.001) and 3.14 (95% C.I. 2.63-3.75, p<0.001) for the 3rd and 4th quartiles, respectively. After adjusting for demographics, hypertension, waist circumference, triglycerides, high-density lipoprotein-cholesterol, homeostasis model assessment-estimated insulin resistance, estimated glomerular filtration rate, and aspartate aminotransferase, uric acid (4th quartile) was significantly associated with NAFLD (odds ratio 1.43; 95% C.I. 1.16-1.76, p<0.001). Positive parameter estimates suggest increasing uric acid is associated with greater severity of NAFLD. CONCLUSIONS: Elevated uric acid level is independently associated with ultrasound-diagnosed NAFLD in a nationally representative sample of United States nondiabetic adults. Increasing uric acid is associated with increasing severity of NAFLD on ultrasonography. These findings warrant further studies on the role of uric acid in NAFLD.
  Metabolism: clinical and experimental 10/2012; · 2.59 Impact Factor