Vascular Inflammatory Processes Research Articles

Inflammatory activation in children with primary hypertension

Low-grade inflammation plays a role in the pathogenesis of primary hypertension (PH) and target organ damage (TOD). We evaluated the profile of inflammatory mediators (CRP, RANTES, MIP-1beta, MIP-1alpha, MCP-1, IL-6, angiogenin, adiponectin) in 30 healthy children (12.7 +/- 3.3 years) and 44 patients with untreated PH (13.7 +/- 2.7 years; n.s). Patients had greater concentrations of CRP, MIP-1beta, and RANTES than controls (all p < 0.05). Children with metabolic syndrome (MS) had greater CRP than children without MS (p = 0.007) and CRP correlated with number of MS criteria, body mass index (BMI), visceral fat, deep subcutaneous fat assessed by magnetic resonance imaging, carotid intima-media thickness (cIMT), left ventricular mass index, and markers of oxidative stress. RANTES correlated with cholesterol, LDL cholesterol, ApoB, and ApoB/ApoA1. Angiogenin correlated with BMI, waist circumference, visceral fat, uric acid, and patients with cIMT>2SD had greater concentration of angiogenin than those with normal cIMT (p = 0.03). Adiponectin was lower in patients with cIMT>2SD than in those with normal cIMT (p = 0.02). No model explaining variability of TOD has been built. Elevated RANTES and MIP-1beta and normal IL-6 and TNF-alpha levels indicate a vascular inflammatory process. Lack of correlation between CRP and chemokines suggests that vascular inflammation in PH precedes the systemic inflammatory changes.

Effect of prostaglandin E1on TNF-induced vascular inflammation in human umbilical vein endothelial cells

Prostaglandin E1 (PGE1) is a member of the prostaglandins and has a variety of cardiovascular protective effects. Increasing attention has been paid to the anti-inflammation activity of PGE1, but little direct evidence has been found. We investigated the effects of PGE1 on cell adhesion and inflammation and the mechanisms responsible for this activity in tumor necrosis factor (TNF)-treated human umbilical vein endothelial cells. Results demonstrated that pretreatment with PGE1 decreased the adhesion between vascular endothelial cells and monocytes, reduced the expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in vascular endothelial cells. In addition, PGE1 suppressed TNF-induced NF-kappaB activation and production of reactive oxygen species. We concluded that PGE1 suppressed the vascular inflammatory process, which might be closely related to the inhibition of reactive oxygen species and NF-kappaB activation in human umbilical vein endothelial cells.

Role of plasminogen activation in neuronal organization and survival

We characterized the interactions between plasminogen and neurons and investigated the associated effects on extracellular matrix proteolysis, cell morphology, adhesion, signaling and survival. Upon binding of plasminogen to neurons, the plasmin formed by constitutively expressed tissue plasminogen activator (tPA) degrades extracellular matrix proteins, leading to retraction of the neuron monolayer that detaches from the matrix. This sequence of events required both interaction of plasminogen with carboxy-terminal lysine residues and the proteolytic activity of plasmin. Surprisingly, 24 h after plasminogen addition, plasmin-detached neurons survived and remained associated in clusters maintaining focal adhesion kinase phosphorylation contrasting with other adherent cell types fully dissociated by plasmin. However, long-term incubation (72 h) with plasminogen was associated with an increased rate of apoptosis, suggesting that prolonged exposure to plasmin may cause neurotoxicity. Regulation of neuronal organization and survival by plasminogen may be of pathophysiological relevance, as plasminogen is expressed in the brain and/or extravasate during vascular accidents or inflammatory processes.

D 008 Association of the Atherosclerosis with tLR2, TLR4 and IL-6 Polymorphisms in Type 2 Diabetics Patients

The importance of different lipid and lipoprotein measurements, including LDL particle concentration and levels of apolipoproteins and triglycerides, in the prediction of future cardiac events continues to be debated. In summary, apo B is a strong, independent predictor of initial and recurrent coronary events, even during statin treatment, and recent studies show its predictive superiority over LDL and non-HDL cholesterol. Importantly, determination of apo B levels is unaffected in a non-fasted or hypertriglyceridemic state and is not derived from other measurements. Thus, clear advantages exist for using apo B as a predictor of CHD. Likewise, triglycerides and triglyceride-rich lipoproteins are also strong, independent predictors of coronary events (initial and recurrent) during statin treatment. Triglycerides or especially triglyceride-rich lipoproteins with apo C-III may provide additional information to apo B. Apo C-III not only impairs lipoprotein metabolism but also stimulates directly the vascular inflammatory process. In contrast, evidence from large epidemiological studies is coalescing toward the view that small LDL size is more of a marker of these atherogenic triglyceride-rich lipoproteins than an independent predictor of CHD. Clearly, there remains considerable interest, both in terms of research and clinical practice, in the role of apo B, triglycerides, and specific apo B-containing lipoprotein particles as independent predictors of CHD risk as well as their potential to improve risk prediction and response to lipid-modifying treatment.

Papel de la aldosterona en las alteraciones vasculares funcionales y en el proceso inflamatorio asociados a la hipertensión en ratas

ObjetivesTo study the participation of aldosterone in the vascular dysfunction, inflammatory process and vascular oxidative stress associated to hypertension. Material and methodsHalf of the group of 22 week-old spontaneously hypertensive rats (n=16) were treated with eplerenone (E-30; 30mg/kg/day) for 10 weeks. Normotensive rats (WKY; n = 8) were used as reference group. Systolic arterial pressure (SAP) was measured by the tail-cuff method. Body weight and heart weight were measured at the end of the treatment. Endothelium-dependent relaxations, as well as vascular mRNA expression of interleukin 1 β and 6 (IL-1β and IL-6), tumor necrosis factor alpha (TNF-α), of endothelial nitric oxide synthase (eNOS), NAD(P)H oxidase subunit p22phox were studied in aorta from SHR untreated or treated with eplerenone. ResultsSHR showed higher levels of systolic blood pressure (p < 0.05) as compare with control rats (199.8±4.2 vs. 125.33±2.0mmHg). Although there were no differences in the body weight among the groups, hypertensive rats had a higher relative heart weight compare to normotensive rats and it was normalize with the treatment of eplerenone (p < 0.05). SHR showed higher vascular mRNA expression of IL-1β, IL-6, TNF-α and p22phox compared to WKY (p < 0.05). Treatment with eplerenone slightly reduced (p < 0.05) blood pressure in hypertensive rats (E30; 181.0±2.0mmHg) and normalized acetylcholine relaxations. Eplerenone enhanced (p < 0.05) eNOS and reduced p22phox, IL-1β, IL-6, TNF-α of aortic mRNA expressions in SHR. ConclusionsIn SHR, aldosterone participates in the functional vascular alterations through the diminution of nitric oxide availability and the enhancement of the inflammatory process and the increase of vascular oxidative stress.

Inhibitory effect of betulinic acid on TNF‐α‐induced adhesion molecule and its related signaling

Vascular inflammation is an important event in the development of vascular diseases including atherosclerosis. In the present study, we investigated whether betulinic acid (BA) inhibits vascular inflammation process induced by tumor necrosis factor‐alpha (TNF‐α) in human umbilical vein endothelial cells (HUVEC). Pretreatment with BA was significantly blocked TNF‐α‐induced expression levels of cell adhesion molecules such as vascular cell adhesion molecule‐1 (VCAM‐1), intracellular adhesion molecule‐1 (ICAM‐1), and endothelial cell selectin (E‐selectin). Gelatin zymography results showed that TNF‐α‐induced metalloproteinase (MMP)‐2 and MMP‐9 activities were prevented by pretreatment with BA. Real time qRT‐PCR data also showed that BA suppressed TNF‐α‐induced increase in VCAM‐1, ICAM‐1, and E‐selectin mRNA expression levels. In addition, BA inhibited the TNF‐α‐induced intracellular reactive oxygen species (ROS) production. Furthermore, pretreatment with BA significantly inhibited the translocation to nucleus and transcriptional activity of NF‐κB increased by TNF‐α. In conclusion, the present data suggested that BA could suppress TNF‐α‐induced vascular inflammatory process, due to the inhibition of ROS and NF‐κB activation in HUVEC.

Effect of ethanol extract of Cynanchum wilfordii on vascular dysfunction in rat fed high fat diet

Hyperlipidemia and hypercholesterolemia are critical pathogenic factors for the development and maintenance of atherosclerosis. This study was designed to investigate whether the ethanol extract of Cynanchum wilfordii (ECW) suppresses atherogenesis in rat fed with high fat diet (HFD). Treatment of HFD with low (100 mg/day/kg) or high (200 mg/day/kg) doses of ECW for 8 weeks markedly attenuated plasma level of triglyceride (TG) and augmented plasma level of high density lipoprotein (HDL)‐cholesterol. Treatment of ECW also lowered the systolic blood pressure (SBP) in atherogenic diet rats. Furthermore, the impairment of acetylcholine (ACh)‐ and sodium nitroprusside (SNP)‐induced relaxation of aortic rings in the HFD‐rat was improved by chronic treatment of ECW. Treatment of ECW also suppressed the HFD‐induced increase in expression levels of intracellular cell adhesion molecule (ICAM)‐1, vascular cellular adhesion molecule (VCAM)‐1, and E‐selectin as well as matrix metalloproteinase (MMP)‐2 in aorta. The decrease in production of cGMP induced by HFD was recovered by administration with ECW in aortic tissue. Taken together, the present study suggests that ECW prevents vascular inflammatory process and vascular dysfunction in rat fed high fat diet.

The Impact of Oral L-Arginine Supplementation on Acute Smoking-Induced Endothelial Injury and Arterial Performance

Smoking is associated with endothelial dysfunction and increased inflammatory status. The amino acid L-arginine, improves endothelial function in patients with cardiovascular risk factors. We investigated the effect of L-arginine on vascular function and inflammatory process in healthy smokers at rest and after acute smoking. We studied the effect of L-arginine and/or placebo in 12 healthy young smokers on three occasions (day 0, day 1, and day 3). The study was carried out on two separate arms, one with L-arginine (3 x 7 g/day) and one with placebo, according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before, immediately after, and 20 min after cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) and as a measure of arterial wave reflections. Serum soluble intercellular adhesion molecule-1 (sICAM-1) was measured. Compared to placebo, L-arginine improved FMD (P < 0.01 at day 1 and P < 0.05 at day 3). L-Arginine reduced PWV and AIx at both days 1 and 3 (P < 0.05 vs. baseline). L-Arginine blunted the acute smoking-induced increase of AIx at both day 1 (P < 0.05) and day 3 (P < 0.01), and prevented the smoking-induced elevation of PWV at day 3 (P < 0.05). Importantly, L-arginine reduced sICAM-1 at days 1 and 3 (P < 0.05 for both vs. baseline). Oral L-arginine improves endothelial function and vascular elastic properties of the arterial tree during the acute phase of smoking, an effect accompanied by reduced sICAM-1 levels in these subjects.

Primary vasculitis of the central nervous system in patients infected with HIV‐1 in the HAART era

Angiitis of the central nervous system (CNS) in patients infected with HIV-1-is often associated with concomitant infection or lymphoproliferative disease of the CNS. Four HAART naïve patients infected with HIV-1 with severe stroke are described. Evidence of vasculitis was found by magnetic resonance angiography. Extensive investigations excluded concomitant opportunistic, lymphoproliferative or autoimmune disorders leading to the diagnosis of primary angiitis of the CNS. Despite initiation of HAART and prolonged suppression of viral replication, these patients remained severely immunosuppressed. The addition of corticosteroids led to a significant improvement of clinical symptoms. Primary angiitis of the CNS should be considered in patients with HIV and stroke. The prognosis of these patients remain poor despite HAART. These observations suggest that the vascular inflammatory process persists despite the control of viral load under HAART in patients with persistent immunosuppression.

Effect of Zanthoxylum schinifolium on TNF-α-induced vascular inflammation in human umbilical vein endothelial cells

Pro-inflammatory cytokines induce the injury of endothelial cells in response to increases of adhesion molecules, leading to vascular inflammation and the development of atherosclerosis. In this study, we evaluated an ethanol extract of Zanthoxylum schinifolium (EZS) to determine if it inhibits the expressions of cellular adhesion molecules in human umbilical vein endothelial cells (HUVEC). When pretreatment of HUVEC with EZS, EZS suppressed the expression levels of cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin induced by TNF-α. The adhesion of HL-60 cells to TNF-α-induced endothelial cells was decreased significantly in a concentration-dependent manner. Furthermore, TNF-α-induced MCP-1 and IL-8 mRNA expression levels were also attenuated by pretreatment with EZS. In addition, EZS suppressed TNF-α-induced production of reactive oxygen species (ROS). EZS inhibited NF-κB activation and IκB-α phosphorylation induced by TNF-α, subsequent degradation of IκB-α. Finally, EZS inhibited TNF-α-induced p38 MAPK and c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these results demonstrate that EZS suppresses vascular inflammatory process, which may be closely related to the inhibition of ROS, JNK, p38 MAPK and NF-κB activation in HUVEC.

Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients

Inflammation is implicated in diabetes and cyclooxygenase (COX) is involved in vascular inflammatory processes, participating in both atherosclerosis and thrombosis. The aims were to determine whether levels of monocyte COX and plasma COX metabolites are increased in Type 1 diabetic patients and to determine whether these could be linked to histone hyperacetylation. Monocytes from 19 Type 1 diabetic and 39 non-diabetic control subjects were probed for COX and acetylated histone H4 proteins by immunoblotting. Plasma COX metabolite levels [thromboxane B(2) (TXB(2)) and prostaglandin E(2) (PGE(2))] were determined by enzyme immunoassay. Monocyte COX-2 expression was significantly up-regulated (1.3-fold) in diabetic relative to the non-diabetic control subjects and plasma PGE(2) was markedly elevated (2.7-fold). In diabetic subjects, monocyte acetylated histone H4 levels were significantly elevated; sub-group analysis indicated that the increased histone acetylation was found only in the complication-free group. Results support increased inflammatory activity in Type 1 diabetes that involves COX-2 and increased prostaglandin production, which may predispose patients to cardiovascular events. The observation of elevated histone acetylation only in complication-free diabetic subjects suggests that this may be a protective mechanism. This merits further investigation as histone hyperacetylation has been associated with reduced expression of factors involved in vascular injury and remodelling.

Inflammation: A Link Between Hypertension and Atherosclerosis

High blood pressure levels are associated with increases in circulating levels of inflammation markers which can reflect vascular inflammatory processes, suggesting that hypertension is a low-grade inflammatory process. The vascular inflammation associated with hypertension could be the link between high blood pressure levels and the atherosclerotic process, which is the principal origin of cardiovascular disease, the leading cause of worldwide mortality. High blood pressure levels are accompanied by increases in oxidative stress due to both higher reactive oxygen specie (ROS) production and reduced ROS scavenging by antioxidant defence. This situation favours endothelial function alterations which allow the expression of adhesion molecules and initiation of fatty streak, the earliest structural change in the atherosclerotic process. At the same time, this inflammation, allows endothelial dysfunction since some inflammatory mediators can negatively affect endothelial cell function. Inflammation, therefore, plays a critical role in development and in complications of the atherothrombotic process. Changes in mechanical stress and activation of humoral factors such as the reninangiotensin- aldosterone system can be underlying not only increases in oxidative stress (and consequently endothelial dysfunction) but also the development of the inflammatory process associated with hypertension.

Anti-Inflammatory Effect ofGastrodia elataRhizome in Human Umbilical Vein Endothelial Cells

Vascular inflammation is a pivotal factor of a variety of diseases, such as atherosclerosis and tumor progression. The present study was designed to examine the anti-inflammatory effect of ethanol extract of Gastrodia elata rhizome (EGE) in primary cultured human umbilical vein endothelial cells (HUVEC). Pretreatment of cells with EGE attenuated TNF-alpha-induced increase in expression levels of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Real time qRT-PCR also showed that EGE decreased the mRNA expression levels of ICAM-1, VCAM-1, E-selectin as well as macrophage chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8). In addition, EGE significantly inhibited TNF-alpha-induced increase in monocyte adhesion of HUVEC in a dose-dependent manner. Furthermore, EGE significantly inhibited TNF-alpha-induced intracellular reactive oxygen species (ROS) production and p65 NF-kappaB activation by preventing IkappaB-alpha phosphorylation. In conclusion, the present data suggest that EGE could suppress TNF-alpha-induced vascular inflammatory process via inhibition of oxidative stress and NF-kappaB activation in HUVEC.

Effect of Buddleja officinalis on High-Glucose-Induced Vascular Inflammation in Human Umbilical Vein Endothelial Cells

In this study, we aimed to investigate whether an aqueous extract of Buddleja officinalis (ABO) suppresses high-glucose-induced vascular inflammatory processes in the primary cultured human umbilical vein endothelial cells (HUVEC). The high-glucose-induced increase in expression of cell adhesion molecules (CAMs) such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) was significantly attenuated by pretreatment with ABO in a dose-dependent manner. Enhanced cell adhesion caused by high glucose in co-cultured U937 and HUVEC was also blocked by pretreatment with ABO. Pretreatment with ABO also blocked formation of high-glucose-induced reactive oxygen species (ROS). In addition, ABO suppressed the transcriptional activity of NF-kappaB and IkappaB phosphorylation under high-glucose conditions. Pretreatment with N(G)-nitro-l-arginine methyl ester (L-NAME), an endothelial nitric oxide (NO) synthase inhibitor, attenuated the protective action of ABO on high-glucose-induced CAM expression, suggesting a potential role of NO signaling. The present data suggest that ABO could suppress high-glucose-induced vascular inflammatory processes, and ABO may be closely related with the inhibition of ROS and NF-kappaB activation in HUVEC.

Genetic Variants of Inflammatory Markers and Arterial Stiffness

Atherosclerotic disease is a primary cause of cardiovascular morbidity and mortality. This disease is generally undiagnosed before the onset of symptoms or complications. Experimental and clinical evidence indicate that inflammation is central to the initiation and progression of atherosclerosis.1 Therefore, vascular inflammation may serve as a potential marker of the disease process itself. Although potentially useful in risk stratification, the current systemic markers of inflammation lack sufficient disease specificity to be used satisfactory as screening tools in cardiovascular disease. The inaccuracy of current inflammatory markers may reflect the fact that these markers are neither derived primarily from the vascular wall nor produced primarily by cells involved in the vascular inflammatory process. Furthermore they may signal inflammation in a number of different organs and tissues, which may or may not have direct implications for the vasculature. Because of heterogeneity of the disease phenotype in the population, a single marker may not provide sufficient biological information for an acute assessment of vascular damage, and, therefore, it may be more interesting to look into a cluster of inflammatory markers. Human studies support an association between inflammatory gene polymorphisms and subclinical and clinical cardiovascular disease.2 The predictive value of arterial stiffness or 1:elasticity for cardiovascular morbidity and mortality has now been very well established.3 Arterial …

Does Tissue Factor Expression by Vascular Smooth Muscle Cells Provide a Link Between C-Reactive Protein and Cardiovascular Disease?

C-reactive protein (CRP) is an acute-phase protein that participates in host defense against bacterial pathogens (reviewed in1,2). It has been used as a biomarker of inflammation, and several studies have shown that it has predictive value for cardiovascular events (reviewed in3). Based on these studies, blood CRP levels are being used increasingly by clinicians to help assess cardiovascular risk and to guide decisions on preventive therapies. CRP levels are also being used as secondary end points in numerous atherosclerosis trials, such as those involving statins. Statins were shown to reduce levels of both low-density lipoprotein (LDL) and CRP in individuals at risk for cardiovascular disease (CVD). This led to a clinical trial that examined the effect of statin therapy on primary prevention in healthy individuals with low LDL cholesterol but elevated CRP levels.4 The results suggested that the ability of statin therapy to reduce inflammation may be as important as its effects on LDL cholesterol in preventing CVD. Despite its value as a predictor of cardiovascular events, it is unclear whether CRP directly contributes to the development and progression of atherosclerotic disease or is simply a marker of the vascular inflammatory process that accompanies atherogenesis. …

Aldosterone and the vascular system

Aldosterone can act in different tissues exerting physiological and pathological effects. At the vascular level, aldosterone affects endothelial function since administration of aldosterone impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorate relaxation to acetylcholine in models of both hypertension and atherosclerosis and in patients with heart failure. A reduction in nitric oxide levels seems to be the main mechanism underlying this effect due to a reduction in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone is a pro-inflammatory factor that can participate in the vascular inflammatory process associated with different pathologies including hypertension through activation of the NFκB system, which mediates the vascular production of different cytokines. This mineralocorticoid also participates in the vascular remodeling observed in hypertensive rats since the administration of eplerenone improved the media-to-lumen ratio in these animals. This effect seems to be due to an increase in extracellular matrix. In summary, aldosterone through mineralocorticoid receptors can participate in the vascular damage associated with different pathologies including hypertension through its prooxidant, pro-inflammatory and profibrotic effects that triggered endothelial dysfunction, an inflammatory process and vascular remodeling.

Effect of Lycopus lucidus on high glucose‐induced vascular inflammation in human umbilical vein endothelial cells

High glucose‐induced vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis. Lycopus lucidus Turcz. has been used as an Oriental traditional medicine and its crude drug is known to have an anti‐inflammatory effect. Thus we investigated whether the aqueous extract of the leaves of L. lucidus Turcz. (ALT) suppresses vascular inflammatory process induced by high glucose in primary cultured human umbilical vein endothelial cells (HUVEC). Western blot analysis revealed that incubation of HUVEC with high glucose increased cell adhesion molecules (CAMs) expression levels, which were significantly attenuated by pretreatment with ALT in a dose‐dependent manner. The enhanced cell adhesion between monocyte and HUVEC induced by high glucose was also blocked by pretreatment with ALT. High glucose induced hydrogen peroxide production and DCF‐sensitive intracellular reactive oxygen species (ROS) formation were also inhibited by pretreatment with ALT. In addition, ALT suppressed the translocation and promoter transcriptional activity of NF‐κB increased in high glucose condition. Taken together, the present data suggested that ALT could suppress high glucose‐induced vascular inflammatory process, which may be closely related with the inhibition of ROS and NF‐κB activation in HUVEC.

An ethanol extract Gastrodia elata inhibits TNF‐α‐induced cell adhesion in human umbilical vein endothelial cells

Gastrodia elata is Oriental herbs that have been widely used for the treatment of inflammatory diseases. Endothelial dysfunction and associated vascular inflammatory processes play pivotal roles in the development of atherosclerosis. The present study was designed to examine the effect of ethanol extract of Gastrodia elata (EGE) on vascular inflammation response in primary cultured human umbilical vein endothelial cells (HUVEC). EGE significantly inhibited tumor necrosis factor‐α (TNF‐α)‐induced increase in monocyte adhesion to HUVEC in dose‐dependent manner. In addition, pretreatment with EGE attenuated the expression levels of cell adhesion molecules such as intercellular cell adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and endothelial selectin (E‐selectin) induced by TNF‐α in HUVEC. Real time RT‐PCR also showed that EGE decreased the expression levels of ICAM‐1, VCAM‐1, E‐selectin, MCP‐1, and IL‐8 mRNA. Furthermore, EGE significantly inhibited the TNF‐α‐induced intracellular reactive oxygen species (ROS) production and NF‐κB activation by preventing IκB phophorylation. In conclusion, EGE has an anti‐inflammatory activity, which is at least in part the result of it reducing the cytokine‐induced HUVEC adhesion to monocytes through the inhibition of intracellular ROS production, NF‐κB activation, and cell adhesion molecules expression in HUVEC.

Anti-Atherogenic Effects of the Aqueous Extract of Rhubarb in Rats Fed an Atherogenic Diet

The present study was designed to investigate whether the aqueous extract of rhubarb (AR) could prevent the development of atherosclerosis through regulating vascular inflammatory processes in rats fed with an atherogenic diet. AR significantly reduced plasma low-density lipoprotein-cholesterol, and increased plasma high-density lipoprotein-cholesterol in rats fed with an atherogenic diet. AR inhibited vascular expressions of endothelin-1 (ET-1) and endothelin-converting enzyme (ECE) induced in rats with an atherogenic diet. On the other hand, AR augmented the vascular expression of endothelial nitric oxide synthase (ecNOS) and restored vascular nitric oxide (NO) production. Furthermore, AR suppressed the elevated expression of vascular nuclear factor-kappaB (NF-kappaB) p65 as well as adhesion molecules, including intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in rats fed with an atherogenic diet. Also, AR decreased endothelial expression of ICAM-1 and ET-1 in aorta. These results suggest that AR suppresses the development of atherosclerosis in the atherogenic-diet rat model through inhibiting vascular expressions of proinflammatory and adhesion molecules via the regulation of nitric oxide and endothelin system.