Van Der Hoorn Research Articles

Manipulation of plant immunity via an mRNA decapping pathogen effector.

This article is a Commentary on McCombe et al. (2023), 239: 222–239.

Book Review Solution Focused Practice Around the World by Kirsten Dierolf, Debbie Hogan, Svea Van Der Hoorn and Sukanya Wignaraja (Editors)

Book Review Solution Focused Practice Around the World by Kirsten Dierolf, Debbie Hogan, Svea Van Der Hoorn and Sukanya Wignaraja (Editors)

Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics.

Elevated low-density lipoprotein cholesterol (LDL-C) is one of the major contributors to cardiovascular heart disease (CHD), the leading cause of death worldwide. Due to severe side effects of statins, alternative treatment strategies are required for statin-intolerant patients. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown great efficacy in LDL-C reduction. Limitations for this approach include the need for multiple injections as well as increased costs associated with patient management. Here, we engineered a DNA-encoded mAb (DMAb) targeting PCSK9 (daPCSK9), as an alternative approach to protein-based lipid-lowering therapeutics, and we characterized its expression and activity. A single intramuscular administration of mouse daPCSK9 generated expression in vivo for over 42 days that corresponded with a substantial decrease of 28.6% in non-high-density lipoprotein cholesterol (non-HDL-C) and 10.3% in total cholesterol by day 7 in wild-type mice. Repeated administrations of the DMAb plasmid led to increasing expression, with DMAb levels of 7.5 μg/mL at day 62. daPCSK9 therapeutics may provide a novel, simple, less frequent, cost-effective approach to reducing LDL-C, either as a stand-alone therapy or in combination with other LDL-lowering therapeutics for synergistic effect.

Turning the spotlight on sexually transmitted infections

Sexually transmitted infections (STIs) represent a heterogeneous group of infections that affect millions of people, including key populations such as sex workers, men who have sex with men, and people who inject drugs. Among them, chlamydia infection and bacterial vaginosis are very common problems, especially in women; it is estimated that one of 12 people in the world has genital infection with herpes simplex virus; the number of cases of syphilis and gonorrhoea is increasing worldwide; and there is an intense debate on how interventions to prevent HIV infection, such as pre-exposure prophylaxis and post-exposure prophylaxis, might have a negative effect on risk taking when it comes to sexual behaviour. Moreover, besides the immediate effect on the health of the infected person, STIs can also lead to infertility, miscarriage, stillbirth, and transmission from mother to child. Overall, WHO estimated that one million new cases of STIs (chlamydia, gonorrhoea, syphilis, and trichomoniasis) occur every day. 1 Newman L Rowley J Vander Hoorn S et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One. 2015; 10: e0143304 Google Scholar Although this number should be hard to ignore, these infections remain a neglected issue in both the public health agenda and the research community. Sexually transmitted infections: challenges aheadWHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. Full-Text PDF Mycoplasma genitalium: yet another challenging STIIn The Lancet Infectious Diseases, Unemo and colleagues1 present a well written and comprehensive Commission on the “challenges ahead” for sexually transmitted infections (STIs). The authors address many issues around some of the most important STIs, such as Chlamydia trachomatis and Neisseria gonorrhoeae, the two most common bacterial STIs globally according to WHO estimates.2 They also address bacterial vaginosis, which is the most prevalent urogenital condition in women worldwide. Although not covered in the Commission because of the availability of recent reviews,3,4 Mycoplasma genitalium infection is a bacterial STI second in prevalence only to C trachomatis in most studies. Full-Text PDF Challenges in responses to syphilis epidemicA decrease in the global estimate of four curable sexually transmitted infections (STIs), including chlamydia, gonorrhoea, trichomoniasis, and syphilis, was observed in 2012 by comparison with that of 2008, but 2015 saw an estimated 357 million new cases for the four infections combined.1 This overall decrease mainly reflects the contribution of the reduction of syphilis seropositivity among pregnant women over time in countries that consistently report seropositivity data to WHO.2 Full-Text PDF Health systems and the new strategy against sexually transmitted infectionsThe Lancet Infectious Diseases Commission by Unemo and colleagues1 on sexually transmitted infections (STIs) is published at an important time in the global public health response to STIs. STIs are important causes of morbidity and mortality. WHO estimated that about 357·4 million new cases of chlamydia, gonorrhoea, syphilis, and trichomoniasis occur annually.2 Viral STIs are also highly prevalent with an estimated 417 million people infected with herpes simplex virus type 2 and approximately 291 million women with human papillomavirus (HPV) infections. Full-Text PDF

EP 37. Hemispheric asymmetries during visually guided force control

Question Over the recent years there has been increasing interest in hand-independent right hemisphere contributions to motor control and factors that impact this recruitment. In this context, the right hemisphere has been associated with the transformation of visual information to guide movements in space ( van der Hoorn et al., 2014 , Serrien et al., 2006 ). Yet, empirical evidence regarding this claim has been limited during motor control. For this reason, the current study employed a visually guided force tracking task with varying spatial and temporal control demands to identify hemispheric activation asymmetries during visuomotor control. Method Hemispheric asymmetries were described with respect to the planning and execution of grip force in 19 young, healthy, right-handed participants. Functional magnetic resonance imaging (fMRI) was performed during the planning and execution of several visually guided force courses with the dominant right and non-dominant left hand. Force courses differed with respect to their spatial and temporal processing demands. Results Results revealed that during planning BOLD responses were indeed right-lateralized in a hand-independent manner in areas associated with visuomotor processing. Yet, importantly this right-lateralization was diminished during actual visually guided grip force execution. Instead, left-lateralization was observed in areas associated with the visually mediated online control of force trajectories (intraparietal sulcus, ventral and dorsal lateral premotor cortex). Further, results revealed left-lateralization in the temporoparietal junction associated with the timing of perceptual events. Conclusion The results suggest that the right-hemisphere is not specialized for visuomotor control per se but particularly the planning of spatial movement features in a visuomotor setting. The left hemisphere, on the other hand, seems to be specialized for the visual-based planning of force timing as well as the online control of visually guided force production. Complementary to the previous literature the here presented results emphasize that the actual movement phase as well as spatial and temporal processing demands are important determinants of hemispheric activation asymmetries during visuomotor control.

The "sensor domains" of plant NLR proteins: more than decoys?

The "sensor domains" of plant NLR proteins: more than decoys?

The global and regional burden of stroke.

The global and regional burden of stroke.

Reporting information retrieval processes: Reply

Many thanks to van der Hoorn and colleagues for their interest in our article and the interesting discussion points. Their comments are very important and deserve to be answered.

Surgical or Medical Management for Asymptomatic Carotid Stenosis

To the Editor: We read with interest the article by Woo et al published in the May issue of Stroke .1 The authors have studied the contemporary results of carotid endarterectomy (CEA) for 5009 asymptomatic carotid stenosis (ACS) identified in the National Surgical Quality Improvement Program database. They have found that the perioperative stroke, death, and myocardial infarction outcome rates are 0.96%, 0.56%, and 0.22%, respectively. The authors have combined the 0.96% perioperative stroke rates with the 5-year stroke risk after …

The Global Burden of Air Pollution on Mortality: The Need to Include Exposure to Household Biomass Fuel–Derived Particulates

Anenberg et al. (2010) demonstrated that global mortality associated with outdoor ozone and particulate matter (PM) exposure has been underestimated and that anthropogenic atmospheric PM rather than ozone is the main contributor to death. Although we acknowledge that their investigation was concerned with outdoor air pollution alone, we feel that attention should be drawn to the burden of disease from household air pollution. Half the world’s population is exposed to fine PM [< 2.5 μm in aerodynamic diameter (PM2.5)] in their own homes as a consequence of using biomass fuels such as wood, charcoal, and animal/crop residues for cooking, lighting, and heating. Such exposure is prolonged, extensive, and overlooked by examination of atmospheric models alone (Torres-Duque et al. 2008). Combustion of biomass fuels has been repeatedly demonstrated to produce high concentrations of domestic air pollution, with PM2.5 exposures extending in to the milligram per cubic meter range, orders of magnitude above concentrations from exposure to anthropogenic particulate pollution outdoors (Regalado et al. 2006). Rural populations, and women in particular, are likely to have particularly high indoor exposures because of the extended time spent on cooking and household activity (Mestl et al. 2007). Anenberg et al. (2010) used exposure– response functions derived from epidemiological studies of outdoor air, which emphasize cardiopulmonary mortality in older cohorts. Household air pollution from biomass fuel combustion contributes to chronic respiratory disease and cardiorespiratory events. However, it is particularly implicated in pneumonia in young children (Dherani et al. 2008) and has been ranked the 11th most important risk factor in global mortality, predominantly because of the association with infection (Ezzati et al. 2004). These early deaths would contribute considerably to the estimate of years of life lost due to PM. We agree with Anenberg et al. (2010) that anthropogenic PM is an important global cause of premature death. However, outdoor levels report only part of the picture and may significantly underestimate the total PM-related mortality burden. Recent work (Pope et al. 2009) has brought together data on exposure–response functions for outdoor air pollution and cigarette smoking, and there is a need for additional similar work to integrate studies on indoor biomass combustion (Ezzati et al. 2000). These studies would help clarify the exposure–response function of household air pollution as well as assist in the important process of identifying the most cost-efficient means of reducing exposure among the 3 billion people who bear the health burden from high particulate concentrations at home.

An Improved Bicistronic CD20/tCD34 Vector for Efficient Purification and In Vivo Depletion of Gene-Modified T Cells for Adoptive Immunotherapy

T-cell-based adoptive immunotherapy is widely used to treat graft rejection and relapse after stem cell transplantation (SCT). However, this approach is hampered by a high risk of life-threatening graft-versus-host-disease (GvHD). Clinical trials have demonstrated the value of suicide genes to modify T cells for the effective control of GvHD. Herewith, we show that the combination of a codon-optimized B-cell antigen (CD20op) with a selection marker based on a cytoplasmic truncated version of the human stem cell antigen CD34 (tCD34) allows the generation of highly enriched gene-modified T cells. We demonstrate coordinate co-expression of both transgenes and high expression of CD20op resulting in an increased susceptibility to Rituximab (RTX)-induced cell death. In addition, T cells partially retained their alloreactive potential and their CD4/CD8 ratio after transduction and expansion. Long-lasting transgene expression was sustained in vivo after adoptive transfer into Rag-1(-/-) mice. Moreover, gene-modified T cells were quickly and efficiently depleted from peripheral blood (PB) and secondary lymphoid organs of transplanted animals after RTX treatment. These results warrant further steps toward a clinical application of CD20op as a suicide gene for adoptive immunotherapy.

Effectors, effectors et toujours des effectors

Effectors, effectors <i>et toujours des</i> effectors

Abstract: P482 NOVEL LXR AGONIST AZ876 REDUCES ATHEROSCLEROSIS WITHOUT INCREASING TRIGLYCERIDES IN PLASMA AND LIVER

P482 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2 NOVEL LXR AGONIST AZ876 REDUCES ATHEROSCLEROSIS WITHOUT INCREASING TRIGLYCERIDES IN PLASMA AND LIVER J van der Hoorn, D Linden, M Bekkers, M Voskuilen, U Lindahl, J Oscarsson, E Lindstedt, H Princen TNO BioSciences, Leiden; AstraZeneca, Molndal Objectives Liver X receptor (LXR) agonists are atheroprotective, but may induce hypertriglyceridemia and liver steatosis. We investigated the effect of the new LXR agonist AZ876 (AZ) on plasma lipids, inflammation and atherosclerosis. GW3965 (GW) was used as a reference. Methods APOE*3Leiden mice were fed an atherogenic diet alone or supplemented with either AZ (5 or 20 μmol/kg) or GW (17 μmol/kg). Effects on plasma parameters and atherosclerosis were assessed after 20 weeks of treatment. Results As compared to control, low dose AZ had no effect on plasma lipids, whereas the high dose AZ increased plasma triglycerides (+150%; p<0.001) and reduced cholesterol (-16%; p<0.05). GW increased plasma triglycerides (+70%; p<0.001). Low dose AZ reduced lesion area (-47%, p<0.05); and high dose AZ strongly decreased lesion area (-91%), the number of lesions (-59%) and lesion severity. In either dose AZ did not affect lesion composition. GW significantly reduced atherosclerosis, but also tended to decrease lesion stability. The atheroprotective effect by high dose AZ and GW were partly explained by their antiinflammatory effects. As low dose AZ did not reduce inflammation markers, the induction of reverse cholesterol transport may be its primary protective action. Signs of liver steatosis were not observed by treatment with low dose AZ or GW. Conclusions We identified a novel LXR agonist that inhibits the progression of atherosclerosis presumably by increasing reverse cholesterol transport rather than by decreasing inflammation, without inducing detrimental lipogenic effects in liver and hypertriglyceridemia. Funding: AstraZeneca provided a grant.

Recipients of the 2009 New Investigator Awards

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 29, No. 5Recipients of the 2009 New Investigator Awards Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBRecipients of the 2009 New Investigator Awards Mark B. Taubman Mark B. TaubmanMark B. Taubman Search for more papers by this author Originally published1 May 2009https://doi.org/10.1161/ATVBAHA.109.187187Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:613–614is corrected byCorrectionThis is the fourth year of competition for ATVB New Investigator Awards. The Awards recognize articles published in ATVB in 2008 that were submitted by new investigators and judged to be the most outstanding in the Atherosclerosis and Lipoproteins, Thrombosis, and Vascular Biology sections of the journal. The three awards are named for Dr Daniel Steinberg, who devised a method to determine the site of degradation of the proteins and lipids of a lipoprotein, which led to the concept of selective uptake of cholesterol and apoprotein that characterizes the reverse cholesterol transport pathway; Dr Karl Link, who identified dicoumarol as the hemorrhagic factor in spoiled sweet clover hay, and then developed dicoumarol and warfarin as anticoagulant drugs; and Dr Werner Risau, who formulated key concepts for the regulation of angiogenesis, challenged the prevailing dogmas about angiogenic factors, and proposed the now accepted hypothesis that several growth factors act sequentially to mediate vasculogenesis, angiogenesis, and vascular remodeling.In the fourth year of the award, 650 papers were submitted for the Awards. Recipients of the awards are:Owen McCarty, PhD, Oregon Health & Science University, the 2009 recipient of the Karl Link New Investigator Award in Thrombosis, for his article “The Thrombin Mutant W215A/E217A Acts As A Platelet GPIb Antagonist” (Arterioscler Thromb Vasc Biol. 2008;28:329–334). Download figureDownload PowerPointOwen McCarty, PhDJosé WA van der Hoorn, PhD, TNO BioSciences/LUMC, the 2009 recipient of the Daniel Steinberg New Investigator Award in Atherosclerosis/Lipoproteins, for her article “Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice” (Arterioscler Thromb Vasc Biol. 2008;28:2016–2022). Download figureDownload PowerPointJosé WA van der Hoorn, PhDMasabumi Shibuya, MD, PhD, University of Tokyo, the 2009 recipient of the Werner Risau New Investigator Award in Vascular Biology, for his article “VEGFR1 Tyrosine Kinase Signaling Promotes Lymphangiogenesis as Well as Angiogenesis Indirectly via Macrophage Recruitment,” (Arterioscler Thromb Vasc Biol. 2008;28:658–664). Download figureDownload PowerPointMasabumi Shibuya, MD, PhDThe recipients will be honored at the 10th Annual Conference on Atherosclerosis, Thrombosis, and Vascular Biology, and will receive a plaque, travel support (provided by the ATVB Council), and a check for $2500, provided by Lippincott, Williams, and Wilkins.The Editors congratulate the recipients of the Awards for their outstanding papers! Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesCorrectionArteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1242-1242 May 2009Vol 29, Issue 5Article InformationMetrics https://doi.org/10.1161/ATVBAHA.109.187187 Originally publishedMay 1, 2009 PDF download Advertisement

Hypertension Management

Elevated blood pressure is a major modifiable risk for cardiovascular disease (CVD) and the leading cause of preventable death worldwide. Current estimates indicate that ≈7.6 million premature deaths and 92 million disability-adjusted life years are attributable to suboptimal blood pressure.1 Most of the lifestyle causes of hypertension are well known, and clinical trials provide clear evidence that reducing blood pressure with antihypertensive drugs significantly decreases CVD morbidity and mortality. Despite this, the World Health Organization is predicting an epidemic of hypertension and, in clinical practice, most patients with hypertension are undiagnosed, untreated, or suboptimally treated.2 Against the backdrop of increasing CVD burden worldwide, the gap between what we know and do in hypertension prevention and management is a major cause for concern. Achieving optimum hypertension control to prevent hypertension-associated CVD has been a substantial challenge. There are multiple reasons for lack of blood pressure control, including health care system characteristics, as well as patient and physician characteristics.3 Treatment and control rates of hypertension are particularly low in most developing countries (typically <10%), and even developed countries have far from ideal levels …

Of Mice and Men

IAn increasing body of evidence suggests that disturbed HDL metabolism increases the risk of cardiovascular disease (CVD).1 HDL metabolism is central to reverse cholesterol transport (RCT), in which excess cholesterol from peripheral tissue is returned to the liver for extracorporeal elimination. HDLs also have non-RCT functions including antiinflammatory, antioxidant, and antithrombotic properties. These may relate collectively to the apoA-I content of HDL particles. A number of therapeutic approaches that target HDL metabolism may be useful in preventing and regressing atherosclerosis and coronary disease.2–3 See accompanying article on page 2016 Among lipid-regulators, niacin (nicotinic acid, vitamin B3, pyridine-3-carboxylic acid) is the most effective therapeutic agent presently available for elevating HDL-cholesterol and apoA-I. Notwithstanding issues with tolerability, niacin has long been available for treating atherogenic dyslipidemias. Data from several clinical trials collectively demonstrate that niacin alone or in combination with other agents, including statins, can reduce cardiovascular events and progression of coronary atherosclerosis.4 The precise therapeutic mechanism(s) of action of niacin remains unclear, but may largely involve a favorable regulation of HDL metabolism. But exactly how it mediates this effect has not yet been elucidated. In this issue of Atherosclerosis, Thrombosis and Vascular Biology , van der Hoorn et al present data in a new animal model on the mechanism of the effect of niacin on HDL metabolism.5 First, they demonstrated that niacin increased plasma HDL-cholesterol concentration in the APOE * 3Leiden.CETP ( E3L.CETP ) mouse model (ie, E3L mice crossbred with human CETP-expressing mice) but not in the E3L model alone. Second, in a matched study design they showed in E3L.CETP mice on a Western-type diet that niacin (118 mg/kg/d, 360 mg/kg/d and 1180 mg/kg/d for at least 3 weeks) dose-dependently increased plasma HDL-cholesterol and apoA-I concentrations by several mechanisms involving reductions in plasma VLDL-triglyceride concentrations and in the …

The Nucleoside Diphosphate Kinase D (NM23-H4) Binds the Inner Mitochondrial Membrane with High Affinity to Cardiolipin and Couples Nucleotide Transfer with Respiration

Nucleoside diphosphate kinase (NDPK/Nm23), responsible for intracellular di- and triphosphonucleoside homeostasis, plays multiple roles in cellular energetics, signaling, proliferation, differentiation and tumor invasion. The only human NDPK with a mitochondrial targeting sequence is NDPK-D, the NME4 gene product, which is a peripheral protein of mitochondrial membranes. Subfractionation of rat liver and HEK 293 cell mitochondria revealed that NDPK-D is essentially bound to the inner membrane. Surface plasmon resonance analysis of the interaction using recombinant NDPK-D and model liposomes showed that NDPK-D interacts electrostatically with anionic phospholipids, with highest affinity observed for cardiolipin. Mutation of the central arginine (Arg-90) in a surface-exposed basic RRK motif unique to NDPK-D strongly reduced interaction with anionic phospholipids. Due to its symmetrical hexameric structure, NDPK-D was able to cross-link anionic phospholipid-containing liposomes, suggesting that NDPK-D could promote intermembrane contacts. Latency assays with isolated mitochondria and antibody binding to mitoplasts indicated a dual orientation for NDPK-D. In HeLa cells, stable expression of wild type but not of the R90D mutant led to membrane-bound enzyme in vivo. Respiration was significantly stimulated by the NDPK substrate TDP in mitochondria containing wild-type NDPK-D, but not in those expressing the R90D mutant, which is catalytically equally active. This indicates local ADP regeneration in the mitochondrial intermembrane space and a tight functional coupling of NDPK-D with oxidative phosphorylation that depends on its membrane-bound state.

Chemical analysis of atherosclerotic plaque cholesterol combined with histology of the same tissue

Sensitive method for chemical analysis of free cholesterol (FC) and cholesterol esters (CE) was developed. Mouse arteries were dissected and placed in chloroform-methanol without tissue grinding. Extracts underwent hydrolysis of cholesteryl esters and derivatization of cholesterol followed by liquid chromatography/mass spectrometry (LC/MS/MS) analysis. We demonstrated that FC and CE could be quantitatively extracted without tissue grinding and that lipid extraction simultaneously worked for tissue fixation. Delipidated tissues can be embedded in paraffin, sectioned, and stained. Microscopic images obtained from delipidated arteries have not revealed any structural alterations. Delipidation was associated with excellent antigen preservation compatible with traditional immunohistochemical procedures. In ApoE(-/-) mice, LC/MS/MS revealed early antiatherosclerotic effects of dual PPARalpha,gamma agonist LY465606 in brachiocephalic arteries of mice treated for 4 weeks and in ligated carotid arteries of animals treated for 2 weeks. Reduction in CE and FC accumulation in atherosclerotic lesions was associated with the reduction of lesion size. Thus, a combination of LC/MS/MS measurements of CE and FC followed by histology and immunohistochemistry of the same tissue provides novel methodology for sensitive and comprehensive analysis of experimental atherosclerotic lesions.

Blood-pressure-related disease is a global health priority

In global-health politics, cardiovascular disease is the elephant in the room—a massive problem that few want to acknowledge and even fewer want to tackle. In today's Lancet, Carlene Lawes and colleagues, on behalf of the International Society of Hypertension, estimate that blood-pressure-related diseases cause about half this burden, killing around 8 million people each year. 1 Lawes CMM Vander Hoorn S Rodgers A et al. for the International Society of HypertensionGlobal burden of blood-pressure-related disease, 2001. Lancet. 2008; 371: 1513-1518 Summary Full Text Full Text PDF PubMed Scopus (1708) Google Scholar Low-income and middle-income countries shoulder about 80% of the cardiovascular-disease burden, half of which is in people of working age. Global burden of blood-pressure-related disease, 2001Most of the disease burden caused by high blood pressure is borne by low-income and middle-income countries, by people in middle age, and by people with prehypertension. Prevention and treatment strategies restricted to individuals with hypertension will miss much blood-pressure-related disease. Full-Text PDF

Adiponectin, Cardiovascular Function, and Hypertension

Hypertension is a major risk factor for cardiovascular disease, and the latter is the leading cause of morbidity and mortality worldwide. In developed countries, hypertension ranks as the top contributing factor for mortality and third in causing disability-adjusted life years.1 Hypertension is a polygenic and complex disease with rising prevalence. More than 25% of the adult population is affected by hypertension, and two thirds of those individuals reside in developing countries.2 Europe shows an even higher prevalence of hypertension than North America.3 With the present trends, the prevalence of hypertension is predicted to increase to 30%, or ≈1.5 billion people, on the globe in the next 20 years.2 Mechanistically, endothelial dysfunction, increased renin-angiotensin system (RAS) activity, and sympathetic nervous system (SNS) hyperactivation have been considered as important risk factors of hypertension and hint at important events taking place at the interface of the endothelium, kidney, and SNS. Obesity is a global epidemic in children and adults. In the United States, a steady increase of the prevalence of obesity has been found in all states.4,5 It is estimated that 65% of the population is overweight, which is judged by body mass index of 25.0 to 29.9, and 30% are obese (body mass index of ≥30.0).6 These numbers have been continuously rising in the past 15 years.7 The National Health and Nutrition Examination Survey III for ≈18 000 adults found that body mass index is an associated risk factor for hypertension independent of age, sex, race, and smoking.8 A long-term weight/hypertension relationship study showed that weight loss of ≈10 kg is associated with a significant decrease of both diastolic and systolic blood pressure.9 Obesity and hypertension are 2 complex disorders that are closely interrelated, but the precise underlying association remains elusive. The uncontrolled …