Procollagen III N-terminal Propeptide Research Articles

Association between blood procollagen III N-terminal propeptide, granulocyte-macrophage colony-stimulating factor and triple therapy in single inhaler efficacy for chronic obstructive pulmonary disease re-exacerbation prevention

Triple therapy with inhaled corticosteroid (ISC) / long-acting β2 agonist (LABA) / long-acting muscarinic antagonist (LAMA) in single inhaler expanded the possibilities for prevention of chronic obstructive pulmonary disease (COPD) exacerbations. Heterogeneity of COPD determines the needs in search of target population and efficacy markers for each existing therapy. Disease phenotype depends on a complex of factors, with respiratory viral infection among the most significant. Aim of the study was to assess the efficacy of triple therapy with ICS/LABA/LAMA in single inhaler for subsequent COPD exacerbations prevention and to search molecular markers of the efficacy depending the etiology of index exacerbation. Material and methods. It was a prospective observational study of three COPD patients’ strata: after COPD exacerbation required hospitalization with viral (n = 60), bacterial (n = 60) and viral-bacterial (n = 60) infection. Triple therapy in single inhaler (n = 104) or in free combinations (n = 76) were prescribed in real clinical practice. COPD was diagnosed according to spirography criteria. To establish the COPD exacerbation etiology the real time PCR of sputum or bronchoalveolar lavage fluid, standard cultural method, blood procalcitonin, as well as marker blood proteins, hyaluronic acid by ELISA measurement were done. Associations were revealed using Cox regression. Results. Triple therapy in single inhaler in comparison with free combinations decreased time to first re-exacerbation, hazard ratio (HR) in viral-associated index exacerbation strata was 0.38 (95% confidence interval (95% CI) 1.15–0.40), in bacterial – 0.47 (0.39–0.72), in viral-bacterial – 0.39 (0.14–0.39). In strata of COPD patients after viral and viral-bacterial exacerbations, in subgroups treated with triple therapy in single inhaler blood procollagen III N-terminal propeptide (PIIINP) (HR for group after viral index exacerbations was 1.03, 95 % CI 1.02–1.28, HR for group after viral-bacterial exacerbations was 1.04, 95 % CI 1.02–1.28), granulocyte-macrophage colony-stimulating factor (GM-CSF) (HR 1.03, 95 % CI 1.02–1.32, 1.01, 95 % CI 1.00–1.35, respectively) content was associated with time of re-exacerbations. Conclusions. Blood PIIINP and GM-CSF during COPD exacerbation are perspective markers of subsequent exacerbations within 1 year in patients after virus-associated or viral-bacterial index exacerbation. In these groups of patients triple therapy in single inhaler is more effective than free combination for subsequent exacerbations prevention.

Changes in Intestinal Flora Structure and Metabolites Are Associated With Myocardial Fibrosis in Patients With Persistent Atrial Fibrillation.

Background: The occurrence of atrial fibrillation is often accompanied by myocardial fibrosis. An increasing number of studies have shown that intestinal flora is involved in the occurrence and development of a variety of cardiovascular diseases. This study explores the relationship between changes in the structure and function of intestinal flora and the progression of myocardial fibrosis in patients with persistent atrial fibrillation.Methods: Serum and stool samples were collected from 10 healthy people and 10 patients with persistent atrial fibrillation (PeAF), and statistical analyses were performed on the subjects' clinical baseline conditions. ELISA was used to measure the levels of carboxy-terminal telopeptide of type I collagen (CTX-I), propeptide of type I procollagen (PICP), procollagen III N-terminal propeptide (PIIINP), fibroblast growth factor-23 (FGF-23), and transforming growth factor-beta 1 (TGF-β1) in serum. Through 16S rRNA sequencing technology, the structural composition of the intestinal flora was detected and analyzed. In addition, metabolomics data were analyzed to determine the differences in the metabolites produced by the intestinal flora of the subjects.Results: By comparing the baseline data of the subjects, it was found that compared with those of the control group, the levels of creatinine (CRE) and serum uric acid (SUA) in the serum of PeAF patients were significantly increased. In addition, we found that the levels of CTX-I, PICP, PIIINP, and TGF-β1 in the serum of PeAF patients were significantly higher than those of the control group subjects. Although the control and PeAF groups exhibited no significant differences in the α diversity index, there were significant differences in the β diversity indexes (Bray-Curtis, weighted UniFrac and Anosim). At the phylum, family and species levels, the community structure and composition of the intestinal flora of the control group and those of the PeAF group showed significant differences. In addition, the compositions of the intestinal metabolites in the two different groups of people were significantly different. They were correlated considerably with PIIINP and specific communities in the intestinal flora.Conclusion: Pathologically, PeAF patients may have a higher risk of myocardial fibrosis. Systematically, abnormal changes in the structure and composition of the intestinal flora in PeAF patients may lead to differences in intestinal metabolites, which are involved in the process of myocardial fibrosis through metabolite pathways.

Dual integrin αvβ3 and αvβ5 blockade attenuates cardiac dysfunction by reducing fibrosis in a rat model of doxorubicin-induced cardiomyopathy

Objective The present study aimed to evaluate the protective role of cilengitide (CGT), an integrin αvβ3 and αvβ5 inhibitor, on doxorubicin (DOX)-induced myocardial fibrosis and cardiac dysfunction in a rat model. Methods. Forty male rats were randomly divided into four groups: DOX (n = 12), intraperitoneal (i.p.) injection of DOX 0.8 ∼ 1.0 mg/kg three times a week for up to 6 weeks, then saline i.p. three times a week for another 3 weeks; CGT (n = 8), CGT 10 mg/kg, i.p. three times a week for 9 weeks; DOX + CGT (n = 12), DOX and CGT co-administration as above for 6 weeks, then CGT alone for another 3 weeks; Control (n = 8), saline i.p. three times a week for 9 weeks. Echocardiography, serum procollagen I C-terminal propeptide (PICP) procollagen III N-terminal propeptide (PIIINP) and C telopeptide type I (CTX-I) were evaluated at baseline and 3, 6 and 9 weeks after initial DOX administration for all surviving rats. The heart tissues were then harvested for myocardial hydroxyproline (HYP) evaluation, qRT-PCR, and western blotting. Results. CGT attenuated DOX-induced eccentric remodeling by improving relative wall thickness at the 9th week. CGT also improved systolic function at the 9th week and diastolic function at the 6th and 9th week. CGT reduced myocardial HYP and serum PICP, PIIINP, CTX-I, and the PICP/PIIINP ratio. RT-PCR and western blot showed that CGT blocked the TGF-β1/SMAD3 pathway and mitigating extracellular matrix turnover. Conclusions. CGT exerted a cardioprotective effect against doxorubicin-induced fibrosis and improved cardiac function.

Procollagen III, N-terminal propeptide (PIIINP): establishment of reference intervals in Northern European adults and children using the MAGLUMI 800 chemiluminescence immunoassay

Procollagen III, N-terminal propeptide (PIIINP) is used as a biomarker for increased collagen III-synthesis. Reference intervals have not been established for the MAGLUMI 800 chemiluminescence immunoassay (CLIA) in Northern European adults or in children. The present study aimed to establish age-specific reference intervals in a Northern European population. PIIINP serum levels were analysed in healthy blood donors 19–67 years (n = 240) and children 2–18 years (n = 420). Furthermore, we investigated total imprecision and stability at room temperature and at −20 °C and performed a method comparison between MAGLUMI 800 CLIA (Snibe Diagnostics, Shenzhen, China) and ADVIA Centaur CP (Siemens Healthcare Diagnostics, Tarrytown, NY,USA). PIIINP was influenced by age but not sex. We established the following reference intervals: 2–10 years, 18–62 µg/L; 11–18 years, 15–75 µg/L; 19–39 years, 15–55 µg/L; 40–67 years, 14–31 µg/L. Total imprecision for PIIINP on MAGLUMI 800 was acceptable with coefficients of variation of 4.9% in the low range and 9.4% in the high range. PIIINP was stable for 24 h at room temperature after centrifugation and for at least 7 months at −20 °C. MAGLUMI 800 yielded significantly higher PIIINP levels than ADVIA Centaur CP. In conclusion, we established age-specific reference intervals for PIIINP using MAGLUMI 800 CLIA in a large Danish cohort. Our results may be useful for other laboratories wishing to establish PIIINP on the same platform and may provide improved guidance for medical doctors treating both children and adults with fibrotic disorders.

Correlation between procollagen propeptides end echocardiography indices in patients with ST segment elevation myocardial infarction (STEMI)

Abstract Objective To investigate the correlation between Procollagen I C-Terminal Propeptide (PICP), Procollagen III N-Terminal Propeptide (PIIINP), indices of echocardiography and anamnestic data in patients with ST segment elevation myocardial infarction (STEMI) and preserved myocardial contractility. Materials and methods 60 men and 23 women diagnosed with STEMI were examined. Echocardiographic studies were performed using SONOS 2500 Cardiac – Vascular Ultrasound (Hewlett Packard, USA). Myocardial contractility was considered to be preserved with left ventricular ejection fraction (LVEF) ≥50%. In addition to standard indices of echocardiography, mitral flow propagation velocity (FPV) was evaluated to diagnose diastolic dysfunction. Coronary angiography was performed using INNOVA 3100 Cardiovascular Imaging System (USA). All patients, during the first twelve hours of the disease, underwent percutaneous coronary intervention (PCI) with stenting of the occluded culprit infarct-related artery. On the 1st and 12th days of hospitalization, the concentrations of PICP and PIIINP were determined for all patients by enzyme-linked immunosorbent assay (ELISA) using laboratory BCM Diagnostics kits (USA). All patients at the hospital received standard therapy. Results The following marker values were obtained: 1st day: PICP 609 (583; 635) ng/ml, PIIINP 26 (18.9; 34.9) ng/ml; 12th day: PICP 588 (580; 561) ng/ml, PIIINP 24.2 (18.6; 30.3) ng/ml. The following significant correlations were revealed: PICP 1st day / isovolumic contraction time – IVCT (m/s) 12th day, r=−0.68, p=0.042; PICP 1st day / Tei Index 12th day, r=−0.72, p=0.028; PICP 1st day / diastolic rigidity 12th day, r=−0.74, p=0.021; PIIINP 1st day/age, r=0.55, p=0.016; PIIINP 1st day/ body mass index (BMI), r=−0.59, p=0.009; PIIINP 1st day / E (cm/s) 1st day, r=0.72, p=0.018; PIIINP 1st day / Em /FPV 1st day, r=0.78, p=0.007; PIIINP 12th day / Em / FPV 1st day, r=0.65, p=0.041; PIIINP 12th day / E (cm/s) 1st day, r=0.67, p=0.033; PIIINP 12th day / E / Em) 12th day, r=0.70, p=0.023; PIIINP 12th day / Em/FPV 12th day, r=0.73, p=0.014. Conclusions The data obtained indicates the correlation between serum markers of myocardial fibrosis and the indices of echocardiography, as well as age. We conclude that, all the markers listed above, are able to represent myocardial remodeling in patients with STEMI. Funding Acknowledgement Type of funding source: None

The relationship between the indicators of the retina condition and other target organ changes in uncomplicated essential hypertension

Background. Changes in retinal microcirculation are considered a subtle indicator of the other target organ damage in hypertension and might have prognostic value. Objective. To establish the relationship between diameters of retinal arterioles and venules, foveal avascular zone (FAZ) area, subfoveal choroid thickness with parameters of left heart and kidneys in middle-aged patients with essential hypertension (EH) stage I-II. Design and methods . A total of 115 people (86 males, 29 females) aged 45-59 years were examined and divided into 2 groups. The main group consisted of 70 patients with EH stage I or II. The control group comprised 45 normotensive practically healthy individuals. Patients with diabetes mellitus, impaired liver function, clinically significant ophthalmic pathology were not included. The following data were analyzed: anamnesis including smoking status; routine blood hemodynamic and biochemical parameters, serum procollagen III N-terminal propeptide (PIIINP); albumin-creatinine ratio in a single morning portion of urine, diurnal albuminuria; parameters of 24-h ambulatory blood pressure monitoring; quantitative electrocardiography (ECG) markers of left ventricular hypertrophy; transthoracic echocardiography; fundus state. Based on the scanning laser ophthalmoscopy, the central retinal arterial (CRAE) and venous (CRVE) equivalents, arteriovenous ratio (AVR) were calculated. Using the method of optical coherence tomography angiography, we determined the FAZ area and subfoveal choroid thickness. Statistical data were processed using the StatSoft Statistica 10. Results. Compared with normotensive individuals, patients with hypertension were characterized by lower values of CRAE (p = 0,009), larger FAZ area (p = 0,019), and comparable values of CRVE, AVR, subfoveal choroid thickness (p > 0,05 for each indicator). Correlation analysis showed that in hypertensive AVR correlated with low-density lipoprotein cholesterol level (r = -0,3; p < 0,05); FAZ area with female gender (r = 0,42; p < 0,05); FAZ area with PIIINP level (r = 0,3; p < 0,05); FAZ area with diurnal albuminuria (r = 0,37; p < 0,05); CRVE with R wave amplitude in aVL lead of ECG (r = 0,31; p < 0,05); CRAE with left atrial volume index (r = -0,3; p < 0,05); subfoveal choroid thickness with age (r= -0,3; p = 0,01). Conclusions. Middle-aged patients with uncomplicated EH are characterized by the lower CRVE values and larger FAZ area compared to normotensive individuals. In EH stage I-II, retinal microcirculation parameters are associated with indicators reflecting the other target organ damage, in particular, the left atrial volume index, R wave amplitude in aVL lead of the standard ECG, diurnal albuminuria, and serum PIIINP concentration.

Dynamics of Parameters of Transmitral Blood Flow and Markers of Myocardial Fibrosis in Patients with Myocardial Infarction

Aim To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods 120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF &lt;50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

Using isotemporal substitution to predict the effects of changing physical behaviour on older adults' cardio-metabolic profiles.

BackgroundIt has been advocated that older adults should concomitantly spend less time in sedentary behaviour (SB), and engage in sufficient physical activity (PA), to reduce their risk of cardio-metabolic diseases. However, it is not clear what intensity of PA must be done to offset SB engagement.AimModel how cardio-metabolic profiles could change if older adults replaced an hour per day (hr·day-1) of a physical behaviour intensity with 1 hr·day-1 of another physical behaviour of a different intensity.MethodsOlder adults (n = 93, 60–89 years old, 55% female) wore a thigh-mounted triaxial accelerometer for seven consecutive free-living days to estimate mean daily hourly engagement in SB, Standing, Light Intensity PA (LIPA), sporadic moderate to vigorous physical activity (sMVPA, bouts <10 continuous minutes), and 10-minute MVPA (10MVPA, bouts ≥10 continuous minutes. Fasting whole blood concentration of plasma glucose, triglyceride, total cholesterol, and glycated haemoglobin (%), along with serum concentration of lipoprotein lipase (LPL), interleukin-6 (IL-6), and procollagen III N-terminal propeptide (PIIINP) were measured.ResultsIsotemporal Substitution, with covariate adjustment, suggested that: total cholesterol concentration could theoretically decrease when 1 hr·day-1 of SB is replaced with Standing, when 1 hr.day-1 of LIPA is replaced with Standing, and when 1 hr·day-1 of sMVPA is replaced with Standing. Triglyceride concentration theoretically decreased when 1 hr·day-1 of SB, Standing, LIPA, or sMVPA is replaced with 10MVPA. Triglyceride concentration theoretically increases when 1 hr·day-1 of 10MVPA is replaced with SB, Standing, or LIPA. No associations with time reallocation appears to exist for LPL, HbA1c, IL-6, and PIIINP.ConclusionThe type of physical behaviour being replaced could be crucial for total cholesterol maintenance. Engagement in 10MVPA could be necessary to improve triglyceride concentration.

Relations between markers of cardiac remodelling and left ventricular collagen in an isoproterenol-induced heart damage model.

There is a great urgency of detecting and monitoring myocardial fibrosis in clinical practice with the aim to improve and personalize therapy against cardiac remodelling. Hence, the aim of this study was to describe alterations in and show potential correlations between the structural characteristics and the molecular and biochemical markers of cardiac remodelling on a model of isoproterenol-induced heart failure. Two groups of 3-month-old male Wistar rats (n = 8 per group) were sacrificed after four weeks of treatment: control (placebo), ISO (5 mg/kg/day intraperitoneally). Chronic ISO treatment led to heart failure (HF) characterized by significant reduction of systolic blood pressure (SBP) accompanied by an increase in left ventricular weight (LVW) along with increased collagen content in the LV. The collagen content correlated negatively with SBP (R = -0.776, P < 0.001) and positively with LVW (R = 0.796, P < 0.001), with Col1a1 (0.83; P < 0.001) and Acta2 (0.73; P < 0.01). Moreover, the mRNA expression of fibrotic remodelling indicator, i.e. TGF-β1 tended to increase, while the level of fibrinolysis markers (MCP-1, TIMP-2, MMP) were unchanged. The plasma markers of collagen, procollagen I C-terminal propeptide (PICP) was 37.34 ± 7.10 pg/mL in control and was reduced by 42% (P < 0.05) in the ISO group and procollagen III N-terminal propeptide (PIIINP) was 1216.7 ± 191.0 pg/mL in control and was decreased by 66% (P < 0.05) in the ISO group. Surprisingly, there was no positive correlation between plasma markers of collagen, i.e. PICP and PIIINP and collagen content or molecular markers of collagen. However, both PICP and PIIINP correlated with BW (R = 0.712, resp. 0.803, P < 0.001), which was significantly reduced (by 25%, P < 0.05) in the ISO group. In conclusion, we assume that the collagen content of the left ventricle does not need unavoidably correlate with plasma markers of collagen, which might be affected by confounding factors in heart failure, such as loss of body weight, presumably associated with a catabolic condition.

Circulating markers of collagen types I, III, and IV in patients with dilated cardiomyopathy: relationships with myocardial collagen expression.

AimsCollagen‐derived peptides such as collagen I C‐terminal telopeptide (CITP) and procollagen III N‐terminal propeptide (PIIINP) have been conventionally used as markers of cardiac fibrosis. Collagen IV 7S domain (P4NP 7S) has been recently reported to be correlated with haemodynamics in patients with acute heart failure. We investigated whether these markers reflect cardiac remodelling and myocardial collagen expression.Methods and resultsIn 80 patients with dilated cardiomyopathy, relationships of CITP, PIIINP, and P4NP 7S to clinical and echocardiographic variables were analysed. CITP and PIIINP were inversely correlated with estimated glomerular filtration rate (r = −0.41, P < 0.001 and r = −0.32, P = 0.004, respectively); P4NP 7S was positively correlated with B‐type natriuretic peptide (r = 0.32, P = 0.003) and γ‐glutamyltransferase (r = 0.38, P < 0.001). These correlations were significant even after adjustment by potential confounders, whereas all three collagen markers were not independently correlated with ejection fraction nor with left ventricular (LV) diastolic diameter. In 33 patients undergoing endomyocardial biopsy, myocardial collagen I and III mRNA expressions were correlated with LV end‐diastolic volume index (r = 0.42, P = 0.02 and r = 0.54, P = 0.002, respectively), whereas myocardial collagen IV mRNA expression was not correlated with LV end‐diastolic volume index nor with ejection fraction. Each collagen‐derived peptide was not significantly correlated with the myocardial expression of their corresponding collagen mRNA.ConclusionsOur study shows that CITP, PIIINP, and P4NP 7S do not reflect myocardial collagen mRNA expression but presumably reflect extra‐cardiac organ injury in heart failure.

Assessment of myocardial fibrosis by late gadolinium enhancement imaging and biomarkers of collagen metabolism in chronic rheumatic mitral regurgitation.

SummaryBackgroundIn chronic rheumatic mitral regurgitation (CRMR), involvement of the myocardium in the rheumatic process has been controversial. Therefore, we sought to study the presence of fibrosis using late gadolinium enhancement cardiac magnetic resonance imaging (LGE–CMR) and biomarkers of collagen turnover in CRMR. MethodsTwenty–two patients with CRMR underwent CMR and echocardiography. Serum concentrations of matrix metalloproteinase– 1 (MMP–1), tissue inhibitor of MMP–1 (TIMP– 1), MMP–1–to–TIMP–1 ratio, procollagen III N–terminal pro–peptide (PIIINP) and procollagen type IC peptide (PIP) were measured. ResultsFour patients had fibrosis on LGE–CMR. PIP and PIIINP concentrations were similar to those of the controls, however MMP–1 concentration was increased compared to that of the controls (log MMP–1 3.5 ± 0.7 vs 2.7 ± 0.9, p = 0.02). There was increased MMP–1 activity as the MMP–1–to– TIMP–1 ratio was higher in CRMR patients compared to the controls (–1.2 ± 0.6 vs –2.1 ± 0.89, p = 0.002). ConclusionMyocardial fibrosis was rare in CRMR patients. CRMR is likely a disease characterised by the predominance of collagen degradation rather than increased synthesis and myocardial fibrosis.

Biomarkers of Inflammation, Thrombogenesis, and Collagen Turnover in Patients With Atrial Fibrillation.

The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF. Baseline plasma was collected from patients with AF prior to ablation surgery at Loyola University Medical Center. Individuals with AF had statistically significantly increased levels of PAI-1, CD40-L, and nucleosomes, when compared to the normal population (P < .0001). Additionally, there was a statistically significant increase in the CRP (P = .01), PIIINP (P = .04), and PIIICP (P = .0008) when compared to normal individuals. From this study, it is concluded that the prothrombotic, inflammatory, and collagen turnover biomarkers PAI-1, CD40-L, nucleosomes, CRP, PIIICP, and PIIINP are elevated in AF.

Tu1751 - Procollagen III N-Terminal Propeptide (PIIINP) as a Circulating Biomarker for Active Stricture Development in Pediatric Crohn's Disease

Tu1751 - Procollagen III N-Terminal Propeptide (PIIINP) as a Circulating Biomarker for Active Stricture Development in Pediatric Crohn's Disease

Clinical outcome, echocardiographic assessment, neurohormonal and collagen turnover markers in low-fl ow severe aortic stenosis with high transvalvular gradient

Patients with severe aortic stenosis (AS), high mean gradient (HMG), and preserved left ventricular ejection fraction (LVEF) may present with paradoxical "low flow" (LF). The aim of the study was to assess the potential effect of cardiac collagen metabolism on the HMG/LF phenomenon in patients with severe AS and to determine a clinical and echocardiographic pattern of these patients. We assessed a clinical status of 89 patients, aged over 64 years, with severe AS, HMG, and preserved LVEF (≥50%). Cardiac structure and function as well as systemic arterial hemodynamics were assessed with echocardiography, conventional Doppler, and tissue Doppler imaging. Moreover, plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), procollagen III N-terminal propeptide (PIIINP), carboxyterminal telopeptide of collagen type I, matrix metallopeptidase 9, and inhibitor of matrix metalloproteinase type 1 were evaluated. We analyzed 2 groups of patients: with normal flow (stroke volume index [SVI], ≥35 ml/m²; n = 70) and with LF (SVI, <35 ml/m²; n = 19). Patients with LF were older, had a larger left atrium and left atrial volume index, smaller aortic valve area, lower energy loss index, stroke work, mitral flow E velocity, mitral annular E' and S' velocities and systemic arterial compliance, higher relative left ventricular wall thickness, E/E', systemic arterial resistance and valvulo-arterial impedance. We observed a correlation between SVI and NT-proBNP, PIIINP, and selected parameters of cardiac structure and function. In patients with severe AS, HMG and preserved LVEF, the LF is related to a more severe obstruction, altered aortic hemodynamics, cardiac dysfunction, and higher blood levels of NT-proBNP. An inverse association between PIIINP and SVI may indicate enhanced tissue fibrosis as an underlying pathology.

Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis.

Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001). In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products.

Aliskiren and perindopril reduce the levels of transforming growth factor-β in patients with non-diabetic kidney disease

It is highly likely that the rise in plasma prorenin and plasma renin during renin inhibitor treatment is induced at least as much by the fall in blood pressure (BP) as it is by the negative feedback of angiotensin II. This could potentially be harmful because high levels of renin and prorenin may stimulate the (pro)renin receptor, thus inducing profibrotic effects. To further understand this relationship, the influence of aliskiren on the urinary excretion of transforming growth factor-β1 (TGF-β1) and procollagen III N-terminal propeptide (PIIINP) was evaluated in patients with nondiabetic kidney diseases. Aliskiren 300 mg and perindopril 10 mg, were each individually administered for 12 weeks separated by a placebo period in a cross-over, randomized, double-blinded pilot study. A 1,131% (P < 0.001) and 628% (P < 0.001) increase in plasma renin concentration was observed after the aliskiren and perindopril therapies, respectively, as compared to the placebo. Aliskiren and perindopril increased prorenin concentrations as compared to the placebo by 100% (P < 0.01) and 52.4% (P = 0.53), respectively. The TGF-β1 excretion was lower after tested therapies compared to the placebo (55.0 ± 7.56 vs. 56.21 ± 8.56 vs. 85.79 ± 14.11 pg/mg creatinine; P = 0.016); without differences between aliskiren and perindopril. PIIINP excretion did not differ between treatments. The study shows that both aliskiren and perindopril suppress TGF-β1 in patients with chronic kidney diseases. This effect was observed despite significant increases in the renin and prorenin concentrations. Further studies involving histological assessments are required to elucidate the exact impact of these agents on renal fibrosis.

Five-year results of elastin and collagen markers as predictive tools in the management of small abdominal aortic aneurysms.

small abdominal aortic aneurysms (AAAs) do rupture and only half of AAAs above 5 cm would have ruptured unoperated. Furthermore, conservative treatment of AAAs may cause psychological side effects and impaired quality of life. To optimise the indication and time for operation for AAAs, we analysed whether serum elastin peptides (EP), procollagen-IIIN-terminal propeptide (PIIINP), and the initial AAA size could predict operation for AAAs in initially conservatively treated AAA. in 1994, 4404 65-73 year old males were invited to hospital-based screening for AAAs by ultrasonography. Seventy-six percent attended. One hundred and forty-one (4.2%) had AAAs (def: +30 mm). Nineteen were offered operation (AAA +50 mm), and 112 were followed with annual control scans for 1-5 years (mean 2.5 years). Of these, 99 had their EP (ng/ml) and PIIINP (ng/ml) determined using ELISA and RIA techniques. Two observers and one scanner were used. the mean expansion rate was 2.7 mm/year. The initial AAA size (r =0.46; 0.26-0.61), EP ( r =0.31; 0.11-0.49), and NPIIIP ( r =0.24; 0.02-0.44) was independently significant associated to expansion rate in a multiple linear regression analysis including the three mentioned variables. The multivariate formula could by ROC curve analysis predict cases reaching 5 cm in diameter within 5 years with a sensitivity and specificity of 91% and 87%, respectively, increasing to 91% and 94%, respectively, by accepting a 2 mm variation in those measurements. Twenty-three were lost to follow up, 21 of these due to death or severe illness. Of these, seven would have been predicted to reach an AAA size recommendable for surgery. If all 23 were included in the analysis, the sensitivity and specificity would have been 87% and 85%, respectively. a predictive model using EP, PIIINP, and initial AAA size seems capable of predicting nine out of 10 AAAs that will be operated on within 5 years. However, a larger sample size is needed for clinical recommendations.