Effect of cardiac lymph flow obstruction on cardiac collagen synthesis and interstitial fibrosis

The effect of chronic cardiac lymphatic obstruction on the myocardial synthesis of collagen type I and III was investigated in a rabbit model. In the lymphatic obstruction group (n=16), plasma C-terminal propeptide type I procollagen (PICP) and N-terminal propeptide type III procollagen (PIIINP) were elevated at 7, 14 and 30 days after the operation (p<0.05). The elevated PICP and PIIINP returned to the pre-operation values 60 days after the operation. The myocardial expression of collagen type I and III mRNA were also enhanced in the lymphatic flow obstruction group. Plasma PICP, PIIINP and myocardial collagen type I and III mRNA remained unchanged in the control group (n=16). We concluded that chronic obstruction of cardiac lymph flow leads to enhanced myocardial collagen synthesis in rabbits. The enhanced collagen synthesis starts within seven days after lymphatic obstruction and subsides after 60 days.     

Cell Death and Serum Markers of Collagen Metabolism during Cardiac Remodeling in Cavia porcellus Experimentally Infected with Trypanosoma cruzi

We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection.     

Circulating Annexin A5 Levels after Atrial Switch for Transposition of the Great Arteries: Relationship with Ventricular Deformation and Geometry

Background

Inflammatory cytokines, cardiomyocyte apoptosis, and altered collagen turnover may contribute to unfavourable ventricular remodeling. This unfavourable ventricular remodelling is well documented in patients after atrial switch operation for complete transposition of the great arteries. We therefore tested if levels of circulating markers of inflammation, apoptosis, collagen synthesis, and extracellular matrix degradation are altered in patients after atrial switch operation for transposition of the great arteries.

Methods and Results

Circulating tumour necrosis factor (TNF)-α, annexin A5 (AnxA5), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined in 27 patients aged 25.2±3.1 years and 20 controls. Ventricular myocardial deformation and left ventricular eccentricity index (EI) were determined by speckle tracking and two-dimensional echocardiography, respectively. Compared with controls, patients had significantly higher circulating AnxA5 (p<0.001) and TNF-α (p = 0.018) levels, but similar PICP, PIIINP, MMP-1 and TIMP-1 levels. For the whole cohort, plasma AnxA5 correlated with serum TNF-α (p = 0.002), systemic ventricular global longitudinal strain (GLS) and systolic and early diastolic strain rate (all p<0.001), and subpulmonary ventricular GLS and early diastolic strain rate (both p<0.001). In patients, plasma AnxA5 level correlated positively with subpulmonary ventricular EI (p = 0.027). Multiple linear regression analysis identified systemic ventricular GLS (β = −0.50, p<0.001) and serum TNF-α (β = 0.29, p = 0.022) as significant correlates of plasma AnxA5.

Conclusions

Elevated plasma AnxA5 level in patients after atrial switch operation is associated with impaired systemic myocardial deformation, increased subpulmonary ventricular eccentricity, and increased serum TNF-α level.     

Changes in serological biomarkers of liver function and connective tissue turnover in chronic hepatitis B during lamivudine therapy

Abstract

Assessment of hepatic damage associated with chronic hepatitis B (CHB) currently relies on measurement of serum transaminases and assessment of hepatic histology. It was determined serum hepatic function tests and the liver fibrosis biomarkers type IV collagen (CIV), amino-terminal propeptide of type I procollagen (PINP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were of value in monitoring the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100?mg lamivudine daily for 48 weeks. Blood samples were obtained at baseline, 24 and 48 weeks. At the end of the treatment period, the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline, alanine aminotransferase, aspartate aminotransferase, PIIINP and the PINP/ICTP ratio and at 24 weeks alanine aminotransferase, aspartate aminotransferase and the PINP/ICTP ratio had lower values in the complete response compared with complete failure groups. Using receiver-operated curve analysis, only the PINP/ICTP ratio at baseline (area under the curve 0.806) and ALT and the PINP/ICTP ratio at 24?weeks (areas under the curve 0.803 and 0.776, respectively) had significant diagnostic ability in detecting responders. In conclusion, the PINP/ITCP ratio is sensitive and specific in detecting responders to treatment.     

External thoracic duct-venous shunt in conscious pigs for long term studies of connective tissue metabolites in lymph

An experimental animal model for lymph studies is described. Thoracic duct-venous shunt was established in 12 pigs. Shunt patency averaged 5.5 days. The composition of connective tissue metabolites in lymph and serum were investigated during a standardized surgical operation (thoracotomy) under general anesthesia. We measured the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) hyaluronan (HA) and total protein. During surgery/anesthesia lymph PICP (p less than 0.04), lymph PIIINP (p less than 0.03) and serum PIIINP (p less than 0.01) and serum PIIINP (p less than 0.03) increased. The changes may be explained by the inactive physical state of the animals. HA showed wide variations, with a tendency like PIIINP. In conscious animals the lymph/serum ratio of PIIINP and HA were 10 and 35, respectively, indicating that lymph is a major route of tissue clearance for these components. The lymph/serum ratio of PICP was 1.0 in conscious pigs, indicating a direct release into the circulation. Total protein in lymph decreased (p less than 0.04) during surgery/anesthesia, whereas no changes were observed in serum. Pigs can be used instead of dogs and sheep in studies on lymph. The effect of surgery/anesthesia must be taken into consideration.     

Changes in serological biomarkers of liver function and connective tissue turnover in chronic hepatitis B during lamivudine therapy

Assessment of hepatic damage associated with chronic hepatitis B (CHB) currently relies on measurement of serum transaminases and assessment of hepatic histology. It was determined serum hepatic function tests and the liver fibrosis biomarkers type IV collagen (CIV), amino-terminal propeptide of type I procollagen (PINP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were of value in monitoring the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100 mg lamivudine daily for 48 weeks. Blood samples were obtained at baseline, 24 and 48 weeks. At the end of the treatment period, the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline, alanine aminotransferase, aspartate aminotransferase, PIIINP and the PINP/ICTP ratio and at 24 weeks alanine aminotransferase, aspartate aminotransferase and the PINP/ICTP ratio had lower values in the complete response compared with complete failure groups. Using receiver-operated curve analysis, only the PINP/ICTP ratio at baseline (area under the curve 0.806) and ALT and the PINP/ICTP ratio at 24 weeks (areas under the curve 0.803 and 0.776, respectively) had significant diagnostic ability in detecting responders. In conclusion, the PINP/ITCP ratio is sensitive and specific in detecting responders to treatment.     

Increased bone turnover is associated with protein and energy metabolism in adolescents with sickle cell anemia

Contribution of bone turnover to the hypercatabolic state observed in sickle cell anemia is unknown. We examined the association between markers of bone turnover and basal rates of whole body protein turnover and energy expenditure in 28 adolescents with homozygous sickle cell anemia (HbSS) and in 26 matched controls with normal phenotype (HbAA). Whole body protein breakdown and synthesis were measured using a stable isotope of [15N]glycine, resting energy expenditure was measured by whole room indirect calorimetry, and the rate of pyridinoline cross-link (PYD) excretion in urine and fasting serum levels of the type I procollagen carboxy-terminal propeptide (PICP) were measured with commercial kits. Urinary PYD and serum PICP were significantly elevated in HbSS patients. The increase in procollagen synthesis, indicated by high levels of PICP, was significantly correlated with increased whole body protein synthesis. The increase in type I collagen degradation, indicated by high PYD excretion, was significantly correlated with increased protein breakdown. We conclude that increased rates of bone turnover contribute to the increased rates of protein turnover and energy expenditure observed in adolescents with homozygous sickle cell anemia.     

骨科损伤控制救治对四肢骨折患者血清骨代谢和炎症反应的影响

为探究骨科损伤控制(damage control orthopaedics, DCO)救治对四肢骨折患者血清骨代谢及炎症反应的影响,本研究选取40例四肢骨折患者,随机分为治疗组和对照组,各20例。治疗组采用骨科损伤控制救治四肢骨折患者,对照组则采用常规骨折治疗方法。酶联免疫法检测试剂盒检测骨代谢指标:骨钙素(bone gla protein, BGP)、Ⅰ型前胶原羧基端前肽(propeptide carboxy-terminal procollagen, PICP)水平、血清碱性磷酸酶(alkaline phosphatase, ALP),骨愈合相关指标:可溶性细胞间粘附分子-1 (soluble intercellular adhesion molecule 1, s ICAM-1)、胰岛素样生长因子-1 (insulin like growth factor-1, IGF-1),以及炎症反应相关因子白细胞介素-1 (interleukin-1, IL-1)、白细胞介素-6 (interleukin-6, IL-6)、肿瘤坏死因子-α(tumor necrosis factor-alpha, TNF-α);统计分析各组患者手术后疼痛程度以及肿胀程度评分。结果表明,骨科损伤控制治疗组的血清骨钙素(BGP)、Ⅰ型前胶原氨基酸末端前肽(PICP)水平、血清碱性磷酸酶(ALP)、可溶性细胞间粘附分子-1 (sICAM-1)和胰岛素样生长因子-1 (IGF-1)水平明显高于对照组;炎症反应因子IL-1、IL-6和TNF-α水平明显低于对照组;骨科损伤控制救治可明显降低四肢骨折患者术后的疼痛程度以及肿胀程度评分。综上所述,骨科损伤控制救治可明显提高四肢骨折患者血清骨代谢和骨愈合水平、降低炎症反应、疼痛以及肿胀程度。     

A cross-sectional study on biochemical parameters of bone turnover and vitamin d metabolites in healthy dutch children and young adults

AIM: To provide reference data of biochemical markers of bone turnover and vitamin D metabolites for children and young adults. METHODS: Blood samples were taken from 176 healthy Dutch children and young adults (age range 7.6-25.3 years) to assess serum calcium, alkaline phosphatase, inorganic phosphate, osteocalcin, collagen type I cross-linked N-telopeptide, N-terminal propeptide of type I procollagen, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 levels. Cross-linked telopeptide of type I collagen and carboxy-terminal propeptide of type I procollagen were assessed in 286 subjects (age range 1.4-25.3 years). RESULTS: Calcium and vitamin D levels were independent of age. The peak concentrations for collagen type I cross-linked N-telopeptide, cross-linked telopeptide of type I collagen, carboxy-terminal propeptide of type I procollagen, N-terminal propeptide of type I procollagen, alkaline phosphatase, and osteocalcin were found during puberty, in girls approximately 2.5 years earlier than in boys. Strong correlations were found between the markers of bone turnover, while no correlation was found between the markers of bone turnover and bone mineral density measured by dual-energy X-ray absorptiometry. CONCLUSIONS: Single measurements of bone markers cannot predict bone density. Reference data according to gender, age, and Tanner stage are given which allow calculating standard deviation scores adjusted for age and gender.     

The N-Terminal Propeptide of Type III Procollagen in Patients with Acute Coronary Syndrome: A Link between Left Ventricular End-Diastolic Pressure and Cardiovascular Events

Background

Despite the usefulness of N-terminal propeptide of type III procollagen (PIIINP) in detecting enhanced collagen turnover in patients with congestive heart failure, the value added by PIIINP to the use of clinical variables and echocardiography in relation to directly measured left ventricular (LV) end-diastolic pressure (EDP) and the outcome of acute coronary syndrome (ACS) has not been clearly defined.

Methods and Results

This study involved 168 adult patients with ACS, who underwent echocardiography, measurement of serum PIIINP levels, and cardiac catheterization. Pulsed wave tissue Doppler imaging (PWTDI), which revealed mean peak systolic (s′), early (e′), and late diastolic (a′) velocities, was carried out and the eas index of LV function was evaluated: e′/(a′×s′). The patients were divided into three study groups based on the degree of LVEDP – normal (<16 mmHg), intermediate (16–30 mmHg), and high (>30 mmHg) LVEDP. All patients were followed-up to determine cardiac-related death and revascularization. Patients with high LVEDP had significantly more PIIINP than those with intermediate or normal LVEDP (all post hoc p<0.05). The presence of coronary artery disease, the left atrial volume index (LAVI), the ratio of transmitral early and late diastolic flow velocities, a′, and the eas index were significantly correlated with LVEDP. According to multiple stepwise analysis, PIIINP, LAVI and the eas index were the three independent predictors of the level of LVEDP (PIIINP, p <0.001; LAVI, p = 0.007; eas index, p = 0.021). During follow-up (median, 24 months), 32 participants suffered from cardiac events, PIIINP and LAVI were significant predictors of cardiac mortality and hospitalization (PIIINP, hazard ratio (HR) 2.589, p = 0.002; LAVI, HR 1.040, p = 0.027).

Conclusions

PIIINP is a highly effective means to evaluate LVEDP in patients with ACS. The PIIINP is also correlated with cardiac mortality and revascularization, providing an additional means of evaluating and managing patients with ACS.     

Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events

PURPOSE OF REVIEW: Disturbances of the synthesis and breakdown of the extracellular matrix of arterial walls have emerged as key features of the atherosclerotic process. Altered levels of circulating extracellular matrix markers have frequently been observed in relation to manifestations of atherosclerotic disease and its risk factors. RECENT FINDINGS: Research has been focused on the matrix-degrading metalloproteinases, their tissue inhibitors, and procollagen peptides. The most promising matrix metalloproteinase is matrix metalloproteinase-9, which has been observed to predict rapid coronary artery narrowing, ischemic heart disease incidence, abdominal aortic aneurysm expansion, worse outcome in stroke patients, and cardiovascular death. The use of tissue inhibitors of metalloproteinases for prognostication is uncertain thus far. The procollagen marker with most prognostic potential is the marker for type III collagen turnover rate, the N-terminal propeptide PIIINP, higher levels of which predict an adverse outcome after a myocardial infarction and in chronic heart failure, and portend abdominal aortic aneurysm expansion and risk of rupture. Also, the marker for type I collagen synthesis, the C-terminal propeptide PICP, predicts adverse outcomes following myocardial infarction and in chronic heart failure. Extracellular matrix remodeling is also a promising therapeutic target, being favorably affected by several conventional cardiovascular drugs and select dietary interventions. Synthetic matrix metalloproteinase inhibitors are also under development. SUMMARY: Circulating matrix markers have emerged as candidate biomarkers for predicting risk of subsequent atherosclerotic events. Future large longitudinal observational and intervention studies will determine the role of matrix biomarkers in diagnosis and prognostication, and as targets for intervention in cardiovascular diseases.     

Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients

BackgroundThere is evidence that diabetic polyneuropathy (PNP) is associated with reduced bone mineral density (BMD) in type 1 diabetes but little is known about the impact of diabetic PNP on bone metabolism in type 2 diabetes.ObjectivesThe aim of this study was to evaluate differences in bone metabolism by measuring markers of bone turnover and BMD in men and postmenopausal women with type 2 diabetes and diabetic PNP compared with those without PNP. Gender differences were analyzed for both groups of patients.MethodsOne hundred twenty patients with type 2 diabetes, 68 without PNP (43 men, 25 women, mean age 62 [8] years) and 52 with PNP (28 men, 24 women, mean age 64 [8] years) were studied. Clinical parameters with bone turnover biomarkers such as osteocalcin, bone alkaline phosphatase, procollagen type 1 amino-terminal propeptide, and carboxy-terminal telopeptide of type 1 collagen were measured in all patients. Dual energy x-ray absorptiometry to evaluate BMD was performed in a subgroup of patients.ResultsAfter controlling for age, body mass index, duration of diabetes, smoking, glycosylated hemoglobin, homeostasis model assessment index for insulin resistance, serum C-reactive protein, creatinine, calcium, gamma-glutamyltransferase, parathyroid and sex hormones levels, presence of micro/macrovascular complications, statin- as well as diabetes-related therapies, levels of carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide were significantly higher among patients with PNP when compared with patients without PNP (P = 0.01 and P = 0.03, respectively). Differences in bone biomarkers were more pronounced among men with diabetes. BMD did not differ significantly between patients with and without PNP, independent of gender.ConclusionsMale patients with PNP exhibit a higher rate of bone turnover than men without PNP. High rate of bone turnover increases the susceptibility for developing osteoporosis. Prevention of diabetic PNP might also reduce the incidence of osteoporosis and fractures in patients with type 2 diabetes.     

Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis.

Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs), which are known to stimulate collagen production in animal tendons, may regulate the translation of mechanical loading to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBP, and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both groups after 72 h and stayed elevated in the exercise group at 96 h (P < 0.05). IGFBP-1 in both serum and dialysate increased in the exercise group immediately after exercise (P < 0.05), whereas IGFBP-3 decreased systemically (P < 0.05). Elevation of local IGFBP-4 was observed in both the control and exercise groups after 48 h (P < 0.05). Total IGF-I did not change in locally or systemically in either group. Our results indicate an increased local production of PICP in human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling technique. Care must therefore be emphasized to minimize the numbers of insertions with microdialysis. We demonstrated an elevation of IGFBP-1 both systemically and peritendinously in response to prolonged acute exercise. The local increased collagen synthesis was preceded by an elevation of local concentration of IGFBP-4, suggesting that IGFBP-4 may have a key role in the IGF-axis effect on the human collagen synthesis in vivo.     

Hormone replacement therapy,calcium and vitamin D<Subscript>3</Subscript> versus calcium and vitamin D<Subscript>3</Subscript>alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.     

Role of TGF-beta1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue.

Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-beta1 (TGF-beta1), a potent stimulator of type I collagen synthesis, is released from cultured tendon fibroblasts in response to mechanical loading. Thus TGF-beta1 could link mechanical loading and collagen synthesis in tendon tissue in vivo. Tissue levels of TGF-beta1 and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)] were measured by microdialysis in peritendinous tissue of the Achilles' tendon in six male volunteers before and after treadmill running (1 h, 12 km/h, 3% uphill). In addition, blood levels of TGF-beta1, PICP, and ICTP were obtained. PICP levels increased 68 h after exercise (P < 0.05). Dialysate levels of TGF-beta1 changed from 303 +/- 46 pg/ml (at rest) to 423 +/- 86 pg/ml 3 h postexercise. This change was nonsignificant, but the decay of tissue TGF-beta1 after catheter insertion was markedly delayed by exercise compared with the decay seen in resting subjects. Plasma concentrations of TGF-beta1 rose 30% in response to exercise (P < 0.05 vs. pre). Our observations indicate an increased local production of type I collagen in human peritendinous tissue in response to uphill running. Although not conclusive, changes in circulating and local TGF-beta1, in response to exercise, suggest a role for TGF-beta1 in mechanical regulation of local collagen type I synthesis in tendon-related connective tissue in vivo.     

Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction.

Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.     

Serum procollagen type III is associated with elevated right-sided filling pressures in stable outpatients with congestive heart failure

Elevated filling pressures are associated with heart failure deterioration, but mechanisms underlying this association remain poorly understood. We sought to investigate whether or not elevated filling pressures are associated with increased collagen turnover, evaluated by procollagen type III aminoterminal peptide (PIIINP) levels, in stable systolic heart failure. Eighty patients with heart failure with severe systolic dysfunction (ejection fraction 26?±?7%) were included. Patients underwent simultaneous echocardiogram with evaluation of haemodynamic parameters and blood sampling for PIIINP measurement. Mean PIIINP level was 6.11?±?2.62 μg l^?1. PIIINP was positively associated with estimated right atrial pressure (RAP) (r?=?0.36; p?=?0.001). Mean PIIINP values were 5.04?±?2.42 μg l^?1 in patients with estimated RAP ≤?5?mmHg, and 7.59?±?2.54 μg l^?1 in those with RAP >?15?mmHg (p?相似文献   

Angiotensin AT2 receptor deficiency after myocardial infarction

Hearts of normotensive angiotensin II type 2 receptor (AT₂)-deficient mice do not develop fibrosis after angiotensin II-induced chronic hypertension. Thus, the goal of our study was to clarify whether AT₂ knockouts (KOs) are also characterized by altered left ventricular (LV) function and modified remodeling of the extracellular matrix (ECM) after induction of myocardial infarction (MI). MI was induced in 5-mo-old female AT₂-deficient mice and controls by occlusion of the left coronary artery. Time-matched sham-operated animals served as controls. After 48 h, the first sets of mice were hemodynamically characterized using a pressure-tip catheter (n=8/group). We also obtained pressure volume loops using a microconductance catheter in additional sets of animals 3 wk after induction of MI (n=7/group). Finally, the collagen index was illustrated by Sirius red staining and quantified by digital analysis. Whereas the LV function of sham-operated animals did not differ between both genotypes, the collagen index was 44% lower in KO animals. Forty-eight hours and 3 wk post-MI, systolic and diastolic LV function were impaired in both AT₂-deficient and wild-type (WT) animals to the same extent by approx 45%. No differences were found between the two genotypes with respect to LV hypertrophy and the fibrosis index in the infarcted and noninfarcted areas 3 wk post-MI. While AT₂-KO mice had less cardiac collagen content under basal conditions, the receptor deficiency had no significant influence on LV function at the two investigated time points after induction of MI or on the remodeling of ECM at the latter time point. Thus, hypetension-induced fibrosis is probably triggered by other control mechanisms than fibrosis induced by MI.     

Localization of precursor proteins and mRNA of type I and III collagens in usual interstitial pneumonia and sarcoidosis

Summary The aim of this study was to assess and compare the accumulation and distribution of newly synthesized type I and III collagens in usual interstitial pneumonia (UIP) and pulmonary sarcoidosis. Lung biopsies from 10 patients with UIP and 13 patients with sarcoidosis were investigated by immunohistochemical technique and mRNA in situ hybridization. The antibodies for the aminoterminal propeptide of type I procollagen and the aminoterminal propeptide of type III procollagen (PINP and PIIINP, respectively) were used. When compared to healthy lung, levels of type I pN- and type III pN-collagens were increased in both of these disorders. Type I procollagen was mostly present as intracellular spots in newly formed fibrosis in UIP while type III pN-collagen was expressed extracellularly underneath metaplastic alveolar epithelium. Type I procollagen was present intracellularly within and around the granulomas of sarcoidosis, whereas type III pN-collagen was expressed extracellularly, mainly around the granulomas. mRNAs of both collagens colocalized with the precursor proteins. We conclude that the expression of precursor proteins and mRNA of type I and type III collagens is increased in UIP and sarcoidosis, reflecting mainly active synthesis of these collagens in different areas of the lung.