Changes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the serum of patients with autoimmune diseases: association with age and disease activity.

Matrix metalloproteinases participate in the degradation of the extracellular matrix proteins and are regulated mainly by their respective tissue inhibitors. In a variety of inflammatory connective tissue diseases, variations in the tissue content of both metalloproteinases and tissue inhibitors have been reported. The purpose of this study was to determine the serum levels of metalloproteinases and tissue inhibitors in patients with autoimmune diseases and compare with those of healthy individuals of similar age. The metalloproteinase content was analyzed by zymography and it was found that the serum levels of metalloproteinase-2 and metalloproteinase-9 of all autoimmune disease samples were decreased, in all diseases examined and independently of clinical activity, while those of active metalloproteinase-9 were significantly elevated. Both tissue inhibitors were quantitated by direct enzyme-linked immunosorbent assay and were also found decreased in autoimmune disease samples, confirming the balance that should exist in the secretion of metalloproteinases and tissue inhibitors. These results suggested that the increased active form of metalloproteinase-9, together with the decreased concentration of tissue inhibitor-2, could be used for diagnostic purposes and for the follow-up of patients with autoimmune diseases.     

Effect of hemodialysis on the plasma level of type IV collagenases and their inhibitors

OBJECTIVES: Increased cell expression of matrix metalloproteinase-9 (MMP-9) was associated with the development of atherosclerosis and osseoarticular tissue destruction in hemodialysis patients. In this study, the pre- and post-HD plasma concentrations of type IV collagenases and their inhibitors in HD patients were examined. DESIGN AND METHODS: Commercial ELISA kits and Zymography techniques were used to assay the parameters in 40 patients pre- and post-HD session. RESULTS: After the hemodialysis process, MMP-9, MMP-2 and TIMP-2 levels were 124 +/- 72, 706 +/- 242 and 248 +/- 90 ng/mL, significantly different from the pre-HD values (187 +/- 148, 759 +/- 304 and 43 +/- 14 ng/mL). TIMP-1 were not affected by HD. Female subjects and patients with chronic glomerulonephritis had higher TIMP-2 than their counterparts (p < 0.05). The effect of gender on MMP-2 levels was interacted with that of membrane types (p < 0.01). CONCLUSION: These results indicated that the hemodialysis process tends to decrease the overall activity of the peripheral plasma MMP system in HD patients.     

Matrix metalloproteinase-9 is elevated in serum of alcohol abusers

BACKGROUND: Moderate alcohol consumption has been shown to protect against coronary heart disease. However, excessive alcohol use has been suggested to have detrimental effects on the cardiovascular system. We examined whether there is an association between alcohol abuse and circulating levels of matrix metalloproteinase-9 (MMP-9), which has been linked to unstable coronary heart disease and arterial inflammation. DESIGN: Serum MMP-9 concentrations were compared between 40 male alcoholics (mean age 42 years) with ethanol consumption > 1000 g week(-1) and 40 social drinker males with an ethanol consumption of < 200 g week(-1) (mean age 45 years). RESULTS: The mean serum MMP-9 concentration was significantly higher in sera of alcoholics compared to control subjects (70.9 +/- 47.7 g L(-1) and 43.1 +/- 19.2 g L(-1), respectively; P = 0.001). Within the alcoholic group, MMP-9 concentration did not correlate with age, gamma glutamyl transferase, carbohydrate-deficient transferrin, aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase. CONCLUSION: Our finding of elevated MMP-9 concentrations in sera of chronic alcohol abusers helps understand the mechanisms of cardiovascular risk among these subjects.     

Increase in the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 in saliva from patients with primary Sjögren's syndrome

BACKGROUND: To investigate the ratio of matrix metalloproteinase (MMP) to tissue inhibitor of metalloproteinase (TIMP) in primary Sj?gren's syndrome (PSS), patients and healthy subjects MMP-2, 9 and TIMP-1, 2 levels were measured in saliva. METHODS: Stimulated whole-mixed saliva was collected from 32 patients and 26 healthy subjects. MMP-2, 9 and TIMP-1, 2 levels were measured using enzyme-linked immunosorbent assay (ELISA) and the sandwich enzyme immunoassay (sandwich EIA). Zymography and reverse zymography were used to identify MMPs and TIMPs. RESULTS: MMP-9 (gelatinase-B) level in saliva was significantly increased in the patients. MMP-9 (ng/ml): patients 231.02 +/- 151.77 (mean +/- S.D.), healthy subjects 145.87 +/- 111.65 (p < 0.05). MMP-2 levels were not detected with this system kit in either healthy subjects or patients. The differences in TIMPs were only trends and not statistically significant (p > 0.05). Accordingly, MMP-9/TIMP-1 was greatly increased in the patients (2.60 +/- 1.18) than in the healthy subjects (1.28 +/- 1.11) (p < 0.01). CONCLUSION: This study found that MMP-9/TIMP-1 and MMP-9 levels in the saliva were significantly higher in pSS patients than those in healthy subjects. Our results indicate that the increase in MMP-9/TIMP-1, rather than the increase in MMP-9, in pSS patients' saliva is strongly involved in destruction of glandular and salivary duct tissues.     

健心颗粒对慢性心力衰竭患者心功能及心肌基质的影响

目的评价健心颗粒对慢性心力衰竭患者心功能及心肌基质的影响。方法 90例慢性心力衰竭患者,随机分为福辛普利组45例(福辛组)与福辛普利加健心颗粒组45例(健心组),采用NYHA心功能分级标准评价2组患者治疗前、后心功能,采用ELISA法测量2组患者血清基质金属蛋白酶(matrix metalloproteinase,MMP)-2,MMP-3,MMP-9及组织金属蛋白酶抑制物-1(tissue inhibitor of metalloproteinase,TIMP-1)水平。结果慢性心力衰竭患者血清MMPs水平与左心室射血分值呈负相关;血清TIMP-1水平与左心室射血分数值呈正相关;福辛组治疗后左心室射血分数值、血清MMP-2,MMP-3,MMP-9及TIMP-1水平与治疗前比较差异无统计学意义(P>0.05);健心组治疗后左心室射血分数及血清TIMP-1水平明显高于治疗前(P<0.05),血清MMP-2,MMP-3,MMP-9水平明显低于治疗前(P<0.05)。结论健心颗粒可通过改善心肌基质而提高慢性心力衰竭患者的心功能。     

2型糖尿病大血管病变患者血清基质金属蛋白酶9及其抑制物1的测定

目的:探讨血清MMP-9及TIMP-1水平与糖尿病大血管病变的关系。方法:采用酶联免疫吸附法对30例正常对照者和54例2型糖尿病患者(其中无合并症糖尿病组29例,合并大血管并发症组25例)血清MMP-9及TIMP-1水平进行检测,分析其与大血管病变的关系。结果:2型DM血清MMP-9、TIMP-1水平与对照组比较显著升高,且随着大血管病变程度呈逐步升高趋势,MMP-9与FBG呈显著正相关(r=0.444,P<0.05),TIMP-1与UAER呈正相关(r=0.395,P<0.05)。结论:认为MMP-9、TIMP-1参与DM大血管病变的发生发展,检测其血清水平可反映DM血管病变的严重程度。     

Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease

BACKGROUND: Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. OBJECTIVES: In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n = 563, age 70+/-6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. RESULTS: Smokers had significantly higher levels of MMP-9 (p<0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p<0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP-9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. CONCLUSIONS: The elevated levels of MMP-9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP-9, TIMP-1 or PAPP-A in the present population.     

MMP-2和MMP-9水平与急性冠脉综合征的相关性临床研究

目的分析基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)在急性冠脉综合征(ACS)中的水平变化及对临床意义。方法随机选取2011年6月至2013年5月期间收治的急性冠脉综合征患者76例作为观察对象,同时选取70例正常人与66例稳定稳定型冠心病患者作为对照,酶联免疫吸附分析法检测血清MMP-2、MMP-9水平,比较MMP-2和MMP-9水平差异性。结果 ACS患者MMP-2为(204.68±38.42)ng/ml,MMP-9为(781.62±287.37)ng/ml,显著高于稳定型冠心病和正常人群(P0.05),其中急性心肌梗死(AMI)患者MMP-2为(276.82±53.86)ng/ml,MMP-9为(793.56±264.38)ng/ml,显著高于不稳定型心绞痛(UA)患者(P0.05)。结论 ACS患者MMP-2和MMP-9呈高表达,MMP-2和MMP-9与急性冠脉综合征关系密切,有望成为预测急性冠脉综合征病情的血清学指标,值得临床深入研究。     

急性髓系白血病82例患者VEGF与MMP-2、MMP-9的相关性研究

为了探讨急性髓系白血病（AML）患者中血管内皮生长因子（VEGF）与基质金属蛋白酶MMP-2、MMP-9的相互关系及二者在AML中的意义，采用半定量RT—PCR技术检测AML患者与正常人骨髓单个核细胞（MNC）MMP-2 mRNA、MMP-9 mRNA、VEOF mRNA的表达，用明胶酶谱的方法测定原代MNC和HL-60细胞分泌的MMP-2、MMP-9的活性。应用ELISA方法检测AML患者血清中VEGF蛋白的水平，分析VEGF和MMP-2、MMP-9 mRNA之间的关系。结果显示：AML患者MMP-2 mRNA、MMP-9 mRNA与VEGF mRNA的表达和VEGF蛋白水平呈正相关，缓解期患者和正常对照无相关性；VEGF阳性组发生髓外浸润率明显高于阴性组；VEOF上调HL-60细胞中bcl-2的表达：结论：AML患者中MMP-2，MMP-9的表达和VEGF具有正相关性，VEGF可以上调部分AML患者中MMP-2，MMP-9的表达，VEOF可能与MMP-2，MMP-9共同参与了白血病髓外浸润的发生。     

心房纤颤模型犬心房组织基质金属蛋白酶9及组织抑制因子1与纤维化的关系

背景：基质金属蛋白酶及其组织抑制因子在心房组织中的相互作用及动态平衡与心房纤颤的发生及维持密切相关。目的：构建持续性心房纤颤犬模型,观察其心房肌组织基质金属蛋白酶9及其组织抑制因子1的基因表达与心房纤颤及心肌纤维化的关系。方法：采用慢性快速心房起搏诱发持续性心房纤颤犬模型,并设置假手术组。通过Masson三色法染色计算胶原容积分数来评估纤维化程度,左心房心肌基质金属蛋白酶9及组织抑制因子1的mRNA水平表达使用反转录聚合酶联反应检测,其蛋白水平表达通过蛋白质印迹法测定。结果与结论：与假手术组相比,持续性心房纤颤模型组心房肌纤维化程度明显增高,胶原容积分数明显增加（P〈0.01）,且基质金属蛋白酶9mRNA及蛋白表达水平明显增加（P〈0.01）,组织抑制因子1的mRNA及蛋白表达水平明显下降（P〈0.01）。结果证实,心房纤颤心房组织中基质金属蛋白酶9/组织抑制因子1基因表达的调控失衡以及基质金属蛋白酶9活性的增高与组织抑制因子1活性降低可能是影响胶原代谢、促进或抑制心肌纤维化,造成心房纤颤时心房结构重构的分子机制之一。     

Immunoreactive N-terminal pro-atrial natriuretic peptide in human plasma: plasma levels and comparisons with alpha-human atrial natriuretic peptide in normal subjects, patients with essential hypertension, cardiac transplant and chronic renal failure

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates

1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume.     

缬沙坦对原发性高血压患者血清P-选择素和基质金属蛋白酶-9水平的影响

目的:观察原发性高血压患者应用缬沙坦治疗前、后血清P-选择素和基质金属蛋白酶-9浓度水平的变化,为原发性高血压患者动脉粥样硬化的防治提供新的实验依据和临床思路。方法:轻、中度原发性高血压患者40例与健康体检者40例(对照组),用ELISA法分别检测其血清P-选择素和基质金属蛋白酶-9的水平。40例高血压病患者进行8周的药物治疗,并观察对上述指标及血压的影响。结果:(1)与对照组比较,高血压患者血清P-选择素及基质金属蛋白酶-9的浓度均增高,差异有统计学意义(P<0.0l)。(2)治疗8周后,高血压患者血清中P-选择素和基质金属蛋白酶-9的浓度均较前下降(P<0.05)。(3)原发性高血压患者血清P-选择素和基质金属蛋白酶-9的Pearson相关系数为0.443,P=0.007(双侧),呈正相关;收缩压、舒张压与血清P-选择素和基质金属蛋白酶-9浓度之间均无线性相关。结论:(1)轻、中度原发性高血压患者血清P-选择素和基质金属蛋白酶-9浓度水平显著增高,二者呈正相关,提示可能存在动脉粥样硬化的发生、发展。(2)缬沙坦可降低轻、中度原发性高血压患者血清P-选择素及基质金属蛋白酶-9水平,这可能是血管紧张素Ⅱ受体阻...     

Serum insulin-like growth factor-axis and matrix metalloproteinases in patients with rheumatic arthritis or rheumatic heart disease

BACKGROUND: Insulin-like growth factor (IGF)-I plays an important role for maintaining cardiac functions. We clarified the unknown role of IGF-axis in rheumatic heart disease (RHD). METHOD: Interleukin (IL)-10, growth hormone (GH), IGF, IGF binding protein (IGFBP)-3 and matrix metalloproteinase (MMP) were measured by ELISA and zymography in 30 age range-matched normal subjects (control), 36 patients with acute phase of rheumatoid arthritis (RA) with positive rheumatoid factor (RF) and C-reactive protein (CRP), and in 43 patients with RHD with negative RF and CRP. RESULT: Compared with normal subjects, increased IL-10 level and decreased GH were found in RA group whereas unchanged IL-10 and decreased GH were found in RHD group. Compared with age range-matched normal subjects, decreased IGFBP-3, MMP-9 levels, unchanged IGF-I were found in RA group whereas decreased IGF-I levels, unchanged IGFBP3 and increased MMP-9 at age>30 years were found in RHD group. IGF-II was not changed in RA and RHD groups. CONCLUSION: These findings may imply that during inflammatory phase, the levels of anti-inflammation was high and total IGF-I and IGF bioavailability were maintained in patients with RA. Our findings in RHD may speculate that the long-term reduction of GH and IGF-I as well as the compensating effects of upregulated MMP-9 activity may be partially involved in the long-term pathogenesis from RHD to heart failure. Decreased GH, decreased IGF-I and increased MMP-9 activities may be possible diagnostic markers in RHD for developing heart failure.     

The Trp64Arg beta3-adrenergic receptor amino acid variant confers increased sensitivity to the pressor effects of noradrenaline in Sardinian subjects

Cardiac parasympathetic control has prognostic significance in heart failure, but the control mechanisms of this system remain poorly defined. We have demonstrated previously a facilitatory role for nitric oxide (NO) in the parasympathetic control of heart rate in young healthy human subjects. In view of the complex abnormalities of regional NO activity observed in chronic heart failure, we now aim to establish if this mechanism is active in subjects with this condition. Groups of 12 heart failure patients [NYHA class II-III; mean age 52 years (range 38-67 years)] and 12 age/sex-matched healthy control subjects [mean age 50 years (range 36-62 years)] were studied. Heart rate variability and baroreflex sensitivity were measured during inhibition of endogenous NO production with N(G)-monomethyl-l-arginine (l-NMMA; 3 mg.h(-1).kg(-1)) and during administration of an equipressor dose of the control vasoconstrictor phenylephrine (12-36 microg.h(-1).kg(-1)). Basal levels of nitrate+nitrite were measured in the plasma as an indication of systemic NO production. In the heart failure patients, despite an equal rise in blood pressure with both drugs, high-frequency indices of heart rate variability increased less with l-NMMA than with phenylephrine: RMSSD (root mean square of successive RR-interval differences) increased by 4+/-2 compared with 26+/-8 ms (P<0.001) and high-frequency power increased by 97+/-62 compared with 1372+/-861 ms(2) (P<0.001). The increases in cross-spectral baroreflex sensitivity were also lower with l-NMMA than with phenylephrine [high-frequency alpha-index, 2.2+/-1.3 and 12.6+/-3.8 ms/mmHg respectively (P<0.001); low-frequency alpha-index, 1.3+/-0.9 and 4.3+/-1.7 ms/mmHg respectively (P<0.05)]. Healthy subjects showed a similar discrepancy in the response of high-frequency indices of heart rate variability to the two drugs, although baroreflex sensitivity responses were significantly different only for the high-frequency alpha-index. Levels of plasma nitrate+nitrite were significantly higher in the heart failure patients compared with controls. These data demonstrate that baroreflex-mediated cardiac parasympathetic activation in human heart failure, as in health, is dependent upon endogenous NO synthesis.     

Increased plasma matrix metalloproteinase-9 levels in migraineurs

BACKGROUND AND OBJECTIVE: Cortical spreading depression and neurogenic inflammation have been hypothesized to be key steps in the development of migraine headache. Recent studies have highlighted matrix metalloproteinase-9 (MMP-9) in cortical spreading depression, neurogenic inflammation, and cerebral ischemia. To seek their possible association, we investigated plasma MMP-9 levels in migraineurs during headache-free periods. METHODS: Plasma MMP-9 levels in 84 migraine subjects and 61 controls were determined by enzyme-linked immunosorbent assay. In addition, 23 patients with tension type headache were included in the study as comparative subjects. RESULTS: The MMP-9 levels in migraineurs (42.5+/-4.6 ng/mL, mean+/-SE) were significantly higher than those in controls (25.4+/-2.7 ng/mL, P< .005). Those levels in tension type headache subjects (24.6+/-4.8 ng/mL) did not differ from those in controls. There was no significant difference between subjects having migraine with aura and those without aura. The MMP-9 levels did not correlate with age, duration of illness, frequency of migraine attack, duration of headache attack, or medication for headache. Mean plasma MMP-9 levels were the highest in subjects from whom blood samples were taken 2-4 days after their latest attack. CONCLUSIONS: The degradation of extracellular matrix showing the increase of MMP-9 in migraineurs may be associated with an abnormality in their blood vessel permeability. MPP-9 plays some role in migraine pathophysiology. Further studies of MMPs are necessary to elucidate their role.     

Differential effects of carvedilol and metoprolol succinate on plasma norepinephrine release and peak exercise heart rate in subjects with chronic heart failure

Dosing equivalency of carvedilol and metoprolol remains a debate. Degree of beta 1-blockade is best assessed by blunting of the exercise-induced heart rate. Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chronic heart failure treated with carvedilol or metoprolol. Thirty-seven subjects treated with carvedilol (32.9 +/- 3.5 mg; n = 23) or metoprolol succinate (XL) (96.4 +/- 15.9 mg; n = 14) referred for cardiopulmonary exercise testing were studied prospectively. Carvedilol versus metoprolol XL subjects did not differ with respect to baseline heart rate (73 +/- 2 vs 70 +/- 3 bpm), or baseline plasma norepinephrine levels (597.5 +/- 78.3 vs 602.1 +/- 69.6 pg/mL), P = NS. However, despite similar peak exercise norepinephrine levels (2735.8 +/- 320.1 vs 2403.1 +/- 371.6 pg/mL), heart rate at peak exercise was higher in subjects receiving carvedilol (135 +/- 4 bpm) than those receiving metoprolol XL (117 +/- 6 bpm), P = 0.02. Similar norepinephrine release and more complete beta 1-blockade is observed in well-matched subjects with chronic heart failure treated with a mean daily dose of metoprolol XL 96.4 mg compared with carvedilol 32.9 mg.     

Effect of angiotensin-converting enzyme inhibition on plasma brain natriuretic peptide levels in patients with heart failure.

1. The aim of this study was to examine the effect of captopril, an angiotensin-converting enzyme inhibitor, on plasma levels of human brain natriuretic peptide-like immunoreactivity (hBNP-li) in patients with congestive heart failure. 2. Six male patients (aged 52-74 years) with mild to moderate congestive heart failure were studied on two occasions in the semi-recumbent position. After a 30 min rest, patients were randomized to receive oral tablets of either captopril (6.25 mg followed by 25 mg 2 h later) or placebo in a single-blind manner. Plasma hBNP-li, atrial natriuretic peptide-like immunoreactivity (ANP-li) and angiotensin II-like immunoreactivity (ANG II-li) levels and blood pressure were measured. 3. Baseline plasma hBNP-li and ANP-li levels in these patients with mild to moderate congestive heart failure were 13.5 +/- 3.2 pmol/l and 50.9 +/- 11.8 pmol/l, respectively. In 11 healthy male subjects aged 20-23 years, the peripheral plasma hBNP-li and ANP-li levels were 1.3 +/- 0.2 pmol/l and 5.6 +/- 1.7 pmol/l, respectively. In all patients, captopril decreased the plasma ANG II-li level (from 24.3 +/- 8.1 to 6.6 +/- 3.2 pmol/l, P < 0.05) and mean arterial blood pressure (from 92 +/- 3 to 80 +/- 3 mmHg, P < 0.05). Compared with placebo, captopril treatment was associated with significant reductions in plasma hBNP-li (from 14.3 +/- 3.0 to 12.8 +/- 2.1 pmol/l, P < 0.05) and in plasma ANP-li (from 53.9 +/- 1.11 to 36.8 +/- 7.6 pmol/l, P < 0.05) levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between atrial natriuretic polypeptide and cyclic 3'5'-guanosine monophosphate in human plasma

To examine the interrelationship between human atrial natriuretic polypeptide (hANP) and cyclic 3'5'-guanosine monophosphate (cyclic GMP), plasma concentrations of these compounds were determined in 61 disease-free humans, as controls, and in 35 patients with congestive heart failure. Levels of plasma hANP (199.6 +/- 53.7 pg/ml) and cyclic GMP (12.6 +/- 1.7 pmol/ml) in patients with congestive heart failure were significantly higher than in the control subjects (hANP 57.1 +/- 2.8 pg/ml, cyclic GMP 5.2 +/- 0.3 pmol/ml). Although plasma hANP concentrations in the patients with congestive heart failure tended to increase with the severity of cardiac dysfunction, there was no significant correlation between the levels of plasma hANP and the grade of heart failure, classified according to the New York Heart Association. However, a significant correlation was found between plasma hANP and cyclic GMP concentrations in both the healthy subjects and the patients with congestive heart failure, and a weak positive correlation between plasma hANP and cyclic 3'5'-adenosine monophosphate (cyclic AMP) concentration in the patients with congestive heart failure. Thus, changes in plasma cyclic GMP concentration depend to some extent on the plasma concentrations of hANP.     

Inverse relationship between markers of nitric oxide formation and plasma matrix metalloproteinase-9 levels in healthy volunteers

BACKGROUND: Nitric oxide (NO) is a major regulator of cardiovascular homeostasis and has anti-atherogenic properties. Reduced NO formation is associated with endothelial dysfunction and with cardiovascular risk factors. Although NO downregulates the expression and activity of the pro-atherogenic enzyme matrix metalloproteinase-9 (MMP-9), no previous clinical study has examined whether endogenous NO formation is inversely associated with the circulating levels of pro-MMP-9, which are associated with cardiovascular events. We examined this hypothesis in 175 healthy male subjects who were non-smokers. METHODS: To assess NO bioavailability, the plasma concentrations of nitrite, nitrate, and cGMP were determined using an ozone-based chemiluminescence assay and an enzyme immunoassay. Pro-MMP-9 and pro-MMP-2 levels were measured in plasma samples by gelatin zymography. RESULTS: We found significant negative correlations between pro-MMP-9 levels and plasma nitrite (P=0.035, rs= -0.159), nitrate (P=0.040, rs= -0.158), and cGMP (P=0.011, rs= -0.189) concentrations. However, no significant correlations were found between pro-MMP-2 levels and the plasma concentrations of markers of NO bioavailability (all P>0.05). CONCLUSIONS: There is an inverse relationship between markers of NO formation and plasma MMP-9 levels. This finding may shed some light on the possible mechanisms involved in the increased cardiovascular risk of apparently healthy subjects with low NO bioavailability or high circulating levels of pro-MMP-9.