Serum levels of aminoterminal type III procollagen peptide and hyaluronan predict mortality in systemic sclerosis.

Systemic sclerosis (SSc) is characterized by an excessive accumulation of collagen in skin and internal organs and increased serum concentrations of different connective tissue metabolites have been reported. In this study of 82 patients with SSc, serum concentrations of aminoterminal type III procollagen peptide (PIIINP), smaller PIIINP-related antigens (Fab PIIINP) and hyaluronan (HA) were increased as compared to healthy controls matched for age and sex. Patients with a shorter disease duration (less than 3 years) had higher serum levels of PIIINP and Fab PIIINP than patients with a longer disease duration. The highest serum concentrations of PIIINP and HA were seen in seven patients who died within 2 years.     

Dupuytren's disease in type I diabetic subjects: investigation of biochemical markers of type III and I collagen

OBJECTIVE: To clarify whether biochemical markers of collagen type III and I metabolism show alterations in type I diabetic subjects with Dupuytren's disease (DD) compared to those without DD. METHODS: DD was assessed in a total of 28 type I diabetic subjects, mean age 43.4 +/- 9.5 (SD) and duration of diabetes 25.2 +/- 9.7 years. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: The prevalence of DD was 32% (9 of 28 diabetic subjects). Average serum ICTP was 2.7 +/- 0.8 micrograms/l in subjects without DD and 3.6 +/- 1.2 micrograms/l with DD (p = 0.0276). No significant association between other collagen markers and DD was found. The reference intervals of PIIINP and ICTP were exceeded only in 1 and 2 subjects, respectively, and they both had DD. CONCLUSION: The degradation of type I collagen might be increased in diabetic subjects with DD. The overall implication was that synthesis or degradation of type III and I collagen in diabetic subjects with DD did not differ enough from those without DD to reflect changes in the biochemical markers of type III and I collagen.     

Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy-terminal telopeptide of type I collagen (ICTP)

This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum C-terminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (>5.0μg/l) in most patients (median 6.6 μg/l, range 1.4–29.4 μg/l). Serum PIIINP was elevated (>4.2μg/l) in 46% (median 4.0 μg/l, range 1.4–20.1 μg/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum β₂-microglobulin (β₂m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP ( P =0.026) and serum osteocalcin ( P =0.036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum β₂m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum β₂m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.     

Increased serum soluble CD40 levels in patients with systemic sclerosis

OBJECTIVE: To determine serum levels of soluble CD40 (sCD40) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCD40 levels were examined by ELISA in 49 patients with SSc, 15 patients with systemic lupus erythematosus, and 26 healthy individuals. sCD40 levels in plasma samples, which were obtained at the same time, were also determined. SSc patients were grouped into 22 patients with limited cutaneous SSc (lcSSc) and 27 patients with diffuse cutaneous SSc (dcSSc). RESULTS: There was no significant difference between sCD40 levels of sera and those of plasma. Serum sCD40 levels were significantly elevated in patients with SSc compared to patients with systemic lupus erythematosus and controls (p < 0.001). Serum sCD40 levels were higher in patients with lcSSc than in those with dcSSc (p <0.001). There was no correlation between sCD40 and sCD40 ligand levels in patients with SSc. CONCLUSION: Elevated serum sCD40 levels were associated with lcSSc. These results suggest that the blockade of CD40/CD40 ligand interaction could be a potential therapeutic strategy in SSc.     

Type III procollagen N-terminal propeptide, soluble interleukin-2 receptor, and von Willebrand factor in systemic sclerosis

OBJECTIVE: To evaluate the blood concentration of type III procollagen N-terminal propeptide (PIIINP), soluble interleukin-2 receptor (sIL-2R), and von Willebrand factor (vWF) in systemic sclerosis (SSc) patients. METHODS: PIIINP, sIL-2R, and vWF were measured in the sera and plasma of 29 SSc patients and 29 sex- and age-matched healthy controls. Serum PIIINP was determined by radioimmunoassay. Both serum sIL-2R and plasma vWF were measured by enzyme-linked immunosorbent assay (ELISA). Associations between concentrations and clinical and laboratory features were evaluated. RESULTS: Serum levels of PIIINP and sIL-2R were significantly higher in the SSc group than in the control group (p < 0.01 for both). No differences in serum PIIINP and sIL-2R levels were found between the limited and diffuse cutaneous subsets. However, PIIINP concentrations were significantly higher in anti-Scl-70 positive SSc patients compared with those of anti-Scl-70 negative patients (p = 0.01). Serum PIIINP levels were significantly higher in SSc patients with restrictive pulmonary function (FVC < 80%) than in patients with normal pulmonary function (p < 0.05). The correlation between PIIINP levels and FVC (p < 0.05) was negative, but the correlation between PIIINP levels and modified Rodnan skin scores (p < 0.05) was positive. sIL-2R levels were not correlated with skin and pulmonary involvement of SSc. There was no difference in vWF levels between those of the SSc patients and those of the control groups. CONCLUSION: These results suggest that serum PIIINP serves as a biologic marker for the extent of skin and pulmonary involvement in systemic sclerosis. Increased serum levels of sIL-2R in SSc patients support a role for T lymphocyte activation in the pathogenesis of systemic sclerosis.     

Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction

In 16 patients with acute myocardial infarction and in 15 controls, procollagen type III aminoterminal peptide in serum (PIIINP) was measured consecutively. Serum PIIINP was increased on the second to third postinfarction day (p less than 0.01) and remained elevated for more than 4 months. Peak values were observed on the third to seventh postinfarction day. The individual peak changes were correlated to infarction size calculated from serum CK-MB and serum lactate dehydrogenase (p = 0.60, p = 0.02). The changes in distribution of PIIINP-related antigens in serum after gel chromatography were similar to changes observed during wound healing in humans. PIIINP is cleaved off procollagen type III during the biosynthesis of type III collagen, which characterizes the early stages of repair and inflammation. Our findings suggest that serum PIIINP reflects the repair processes and scar formation following acute myocardial infarction. The serum PIIINP alterations in acute myocardial infarction differ essentially from the changes in myocardial enzymes reflecting myocardial injury. Serum PIIINP may therefore provide new and clinically relevant information on the healing of myocardial infarction.     

CARBOXYTERMINAL TYPE I PROCOLLAGEN PEPTIDE CONCENTRATIONS IN SYSTEMIC SCLEROSIS: HIGHER LEVELS IN EARLY DIFFUSE DISEASE

Systemic sclerosis (SSc) is characterized by increased collagendeposition in skin and internal organs, and increased serumconcentrations of different connective tissue metabolites havebeen reported. In this study serum concentrations of carboxyterminaltype I (PICP) and aminoterminal type III procollagen peptide(PIIINP) were higher in 24 patients with diffuse cutaneous systemicsclerosis (dSSc), than in 30 patients with limited cutaneoussystemic sclerosis (lSSc). Thirty patients with advanced andprogressing disease had higher serum concentrations of bothpeptides than 24 patients with milder disease. In patients withadvanced disease, both peptides showed a negative correlationto disease duration. Despite being relatively higher both inearly, widespread and advanced disease, serum PICP concentrationsvaried only within the normal range for healthy controls. ThusPICP is of limited value as a marker of disease activity inSSc. KEY WORDS: Procollagen peptide, Collagen, Aminoterminal type III procollagen peptide, Scleroderma     

Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal controls

BACKGROUND: Excess tissue matrix accumulates in systemic sclerosis (SSc), accounting for both visceral and dermal fibrosis. It is suggested that decreased serum levels of matrix metalloproteinases (MMPs) or increased levels of tissue inhibitors of matrix metalloproteinases (TIMPs) may account for this matrix accumulation. OBJECTIVE: To measure serum levels of tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and collagenase-1 (MMP-1), in patients with diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), primary Raynaud's phenomenon (RP), and in normal controls. METHODS: Serum samples from patients with dcSSc (n=83), lcSSc (n=87), RP (n=80), and normal controls (n=98) were analysed using enzyme linked immunosorbent assays (ELISAs) for total TIMP-1, TIMP-2, and MMP-1. Results from each assay were analysed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups. RESULTS: TIMP-1 levels were significantly raised in dcSSc and lcSSc groups compared with the RP group and normal controls (p<0.01 to p<0.001). In the dcSSc group, TIMP-1 levels were significantly higher in early disease (<2 years) than in late stage disease (>4 years) (p<0.05). This was not found for the lcSSc group. Serum TIMP-2 and MMP-1 levels in dcSSc and lcSSc did not differ significantly from those in normal controls. Increased levels of TIMPs were not convincingly associated with organ disease. No assay result correlated with autoantibody status (anti-topoisomerase 1 (anti-Scl-70), anticentromere antibody, or anti-RNA polymerase). No significant differences in serum TIMP-1, TIMP-2, or MMP-1 levels were shown in the RP group compared with normal controls. CONCLUSIONS: Raised TIMP-1 levels in the SSc groups support the hypothesis that matrix accumulation occurs in SSc at least in part owing to decreased degradation. Moreover, the variation in TIMP-1 levels between the early and late disease stages of dcSSc seems to reflect the early progressive course of dermal fibrosis seen clinically. The expected reduction in serum MMP-1 levels in the SSc groups was not found. This suggests that tissue matrix accumulation is due to increased inhibitors rather than to decreased MMPs.     

Myocardial collagen metabolism in failing hearts before and during cardiac resynchronization therapy

BACKGROUND: In patients with heart failure cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling. AIM: To evaluate whether myocardial collagen metabolism in patients with heart failure is implicated in adverse ventricular remodelling and response to CRT. METHODS: Collagen synthesis and degradation were assessed from the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with heart failure before and after 6 months of CRT. Forty-six patients (72%) showed a > 10% reduction in LV end-systolic volume at follow-up and were classified as responders to CRT, the other 18 patients (28%) were classified as non-responders. RESULTS: Responders demonstrated a mean (+/-SEM) increase of serum PINP and PIIINP during follow-up, from 32.9+/-2.2 to 46.7+/-4.0 microg/L (p < 0.001) and from 4.59+/-0.24 to 5.13+/-0.36 microg/L (p < 0.05), respectively. In non-responders, serum PINP and PIIINP remained unchanged during follow-up. At baseline, responders had significantly lower serum PINP than non-responders (32.9+/-2.2 vs. 41.8+/-4.3 microg/L; p < 0.05). ICTP levels of responders at baseline tended to be higher than in non-responders (3.54+/-0.56 vs. 2.08+/-0.37 microg/L, p = ns), and in both groups ICTP levels did not change upon CRT. CONCLUSION: Reverse LV remodelling following CRT is associated with increased collagen synthesis rate in the first 6 months of follow-up.     

Bioactivity of prolactin in systemic sclerosis

OBJECTIVES: To evaluate basal serum prolactin (PRL) levels in systemic sclerosis (SSc) patients with different degrees of skin involvement, and investigate its relationship with some of the clinical and serological parameters of the disease. METHODS: Basal serum PRL was measured in 44 SSc patients (38 F, 6 M) using a rat NB2 lymphoma line cell proliferation assay. Other parameters measured were: serum aminoterminal propeptide of type III procollagen (PIIINP) by RIA; soluble alpha interleukin-2 receptor (IL-2 sRalpha), serum intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF) by ELISA; the erythrocyte sedimentation rate (ESR); and C-reactive protein (CRP). Skin and organ/system involvement were assessed according to Medsger et al.'s organ/system severity scale, and global disease activity index according to Valentini et al. RESULTS: The serum PRL concentration in the SSc patients was 13.8 ng/ml (95%CI from 3.2 to 49.1 ng/ml), similar than that in control subjects (12.8 ng/nl: 95%CI 3.0 to 18.4 ng/ml). Hyperprolactinemia, defined as a level > 20 ng/ml (mean 30.9 ng/ml, median 29.3) was found in a total of 6 cases (13.6%; 95%CI 5.8 to 28%) cases: in 1 out of 6 men (16.7%; 95%CI -26% to 59%) and similarly in 5/38 women (13.2%; 95%CI 1.9% to 24.4%). No correlation was found between PRL levels and SSc subgroup (lcSSc, icSSc, dcSSc), serologial parameters, or the level of disease activity. Finally, no significant correlations were found with clinical or serological variables. CONCLUSIONS: The findings confirm that mild hyperprolactinemia occurs in at subgroup of SSc patients. However, prospective studies are needed to better define the relationship between PRL and disease activity in scleroderma.     

Application of markers of collagen metabolism in serum and synovial fluid for assessment of disease process in patients with rheumatoid arthritis.

OBJECTIVE--To assess the potential of markers of collagen metabolism to reflect disease processes in rheumatoid arthritis (RA). METHODS--Serum (S) and synovial fluid (SF) from 59 patients with RA, and a knee joint effusion and serum from 90 control subjects were studied with radioimmunoassays for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively). The breakdown of type I collagen was quantified with a radioimmunoassay for the cross linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS--About 50% of the patients had increased S-ICTP and S-PIIINP values, whereas S-PINP was increased in only 20% of the patients. The mean SF:S ratios of these markers varied between 4 (for ICTP) and 340 (for PIIINP), indicating that markers of collagen metabolism are formed locally and then released into the circulation. SF-PINP and SF-PIIINP correlated with each other (rs = 0.86, p < 0.001) and with SF-ICTP (rs = 0.69, p < 0.001, and rs = 0.65, p < 0.001, respectively). SF-ICTP was clearly related to radiographic findings in the corresponding knee joint, patients with gross bone deformation having the greatest SF-ICTP concentrations. S-ICTP and S-PIIINP also correlated with conventional markers of disease activity, such as C reactive protein and joint swelling score. CONCLUSION--Markers of collagen metabolism both in serum and synovial fluid can be measured to provide an assessment of disease process in patients with RA. ICTP and PIIINP are the most informative.     

Biochemical markers of types I and III collagen and limited joint mobility in type 1 diabetic patients

Abstract. Limited joint mobility (LJM), a long-term complication of diabetes, has been shown to be associated with microvascular complications of diabetes. Connective tissue alterations may contribute to the development of LJM and other diabetic complications. We tested whether biochemical markers of types I and III collagen metabolism are associated with LJM in type 1 diabetes. We studied 28 male patients of mean age 43.4 years (SD=9.5) and with a duration of diabetes of 25.2 years (SD=9.7) years. LJM assessment included goniometric measurements of the joints and classification by Rosenblooms method. We measured serum concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP); urinary excretion of crosslinked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) was also measured. Although average serum PIIINP tended to be higher in subjects with moderatesevere LJM (3.1±1.3 µg/l) than in subjects with mild LJM (2.5±0.7 µg/l) or without LJM (2.6±0.4 µg/l), no significant association was found (p<0.27). Concentrations of the other collagen markers were not different in subjects with or without LJM. We conclude that synthesis and degradation of types I and III collagen in diabetic subjects with LJM did not differ from those without LJM to reflect changes in the biochemical markers of these proteins.     

Abnormal bone turnover in monoclonal gammopathy of undetermined significance: analyses of type I collagen telopeptide,osteocalcin, bone-specific alkaline phosphatase and propeptides of type I and type III procollagens

Abstract: The main difference between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is the presence of lytic bone destructions in the latter. About 20% of MGUS patients develop MM, and histomorphometric studies have shown disturbed bone turnover rates in some of these patients. This study was performed in order to evaluate whether serum analyses of the C-terminal telopeptide of type I collagen (ICTP), as a reflector of bone degradation, and of osteocalcin, bone-specific alkaline phosphatase (bAP) and the C-terminal propeptide of type I procollagen (PICP), as markers of bone formation, might give information on disturbancies of bone metabolism in MGUS. Furthermore, serum N-terminal propeptide of procollagen III (PIIINP) might give information on disturbances in collagen III metabolism in the bone marrow. In the 35 patients examined, serum ICTP was elevated in 12 patients (34%), serum PIIINP elevated in 6 patients (17%), serum osteocalcin elevated in 11 patients (31%), serum bAP elevated in 6 patients (17%), and serum PICP elevated in 4 patients (11%). Serum ICTP correlated significantly with PIIINP (r=0.72, p<0.001), and with serum osteocalcin (r=0.57, p<0.001) and serum bAP (r=0.51, p=0.002). These findings indicate disturbancies of bone turnover and affected collagen metabolism in some MGUS patients. Follow-up observation may reveal any prognostic value of these findings.     

Serum levels of soluble CD21 in patients with systemic sclerosis

Systemic sclerosis (SSc) is a systemic disorder that typically results in fibrosis of the skin and multiple internal organ systems. Although the precise mechanism is unknown, overproduction of extracellular matrix proteins, including collagens and fibronectins, and aberrant immune activation might be involved in the pathogenesis. The soluble cluster of differentiation 21 (sCD21) represents the extracellular portion of the CD21 glycoprotein that is released by shedding from the cell surfaces into plasma. sCD21 binds complement fragments and activates monocytes through binding to membrane CD23. The present study was undertaken to investigate the serum levels of sCD21 in patients with SSc. Serum sCD21 levels were reduced with age both in patients with SSc and normal controls. Serum sCD21 levels in patients with SSc were significantly decreased compared to those in control subjects. When we divided patients with SSc into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), patients with lcSSc had lower levels of serum sCD21 than those with dcSSc. Moreover, the prevalence of pulmonary fibrosis in the patients with dcSSc inversely correlated with serum sCD21 levels. Our finding may support the notion that B-cell activation is involved in the mechanism for pulmonary fibrosis and skin sclerosis.     

Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis

OBJECTIVES: To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in patients with dcSSc or lcSSc were significantly lower than those in normal controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2 +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference in the serum MMP-13 levels between patients with dcSSc and those with lcSSc. Disease duration prior to the diagnosis was significantly shorter in SSc patients with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2 vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately correlated with the duration of the disease (r = 0.451, P < 0.05). Though there was no significant difference in the frequencies of pulmonary fibrosis or reduced %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced %VC (vital capacity) was significantly greater in patients with decreased serum MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05). CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may serve as a useful marker for the severity of pulmonary fibrosis in patients with SSc.     

Assessment of relationship between secretion of melatonin, activity of thyroid, adrenal cortex as well as testes and chosen markers of collagen metabolism in starved rats

In starved rats the mutual interrelations were studied between the secretion of melatonin (MEL), thyroid hormones (TT[_4], FT[_4], TT[_3], FT[_3], rT[_3]), corticosterone (B), testosterone (T) and some markers of collagen metabolism: serum concentrations of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) (determined by RIA method) as well as urine concentration of hydroxyproline (OH-Pr) (determined by colorimetric method). Starved rats were found to have significantly increased serum MEL, B, and rT[_3] concentrations while serum values of TT[_4], FT[_4], TT[_3], FT[_3], T and PICP as well as urinary OH-Pr were significantly decreased. The concentrations of PICP, PIIINP and OH-Pr correlated negatively with MEL and B values, but positively with TT[_4] and FT[_4]. It was concluded that starving may change the collagen metabolism in rats indirectly via a modulating effect of changes in MEL, thyroxine and corticosterone.     

Collagen synthesis in postmenopausal women during therapy with anabolic steroid or female sex hormones

The effect of anabolic steroid therapy and estrogen-progestogen substitution therapy on serum concentration of procollagen type III aminoterminal peptide (PIIINP), a measure of collagen synthesis, in postmenopausal women was studied in two double-blind studies: (1) 39 women allocated to treatment with either 50 mg nandrolone decanoate as an intramuscular depot or placebo injections every third week for 1 year, and (2) 40 women allocated to receive either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate daily or placebo tablets for 1 year. Serum PIIINP was measured every 3 months during the study. Anabolic steroid therapy resulted in a more than 50% increase (P less than .001) in serum PIIINP at 3 months, which thereafter decayed but remained significantly increased throughout the study period. Serum PIIINP showed the same pattern during estrogen-progestogen therapy, but to a lesser degree. We conclude that anabolic steroids stimulate type III collagen synthesis in postmenopausal women, while estrogen-progestogen therapy may have such an effect, but only to a lesser degree.     

Influence of primary coronary intervention on myocardial collagen metabolism and left ventricle remodeling predicted by collagen metabolism markers

The aims of the present study were to analyze cardiac collagen metabolism changes in vivo during acute and nonacute phases of ST elevation myocardial infarction (STEMI) in patients who were treated with primary coronary intervention (PCI) only, and to determine the predictive significance of collagen I and III synthesis markers (PICP, PIIINP) as well as the collagen I degradation marker (ICTP) on left ventricular function and volume changes after STEMI. Serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) assessed on the 30th day and the carboxyterminal telopeptide located at the C end of collagen type I (ICTP) assessed on the 7th day after STEMI were significantly higher (P = 0.01, P = 0.019, P = 0.04, respectively) in the PCI unsuccessful group than in the PCI successful group. These findings support the theory that early and successful PCI not only limits the amount of muscle necrosis but also protects cardiac collagen from ischemia-related injury. PICP and PIIINP levels assessed on the fourth day after acute STEMI enables us to predict the development of left ventricular function (EF) and end-diastolic volume changes over the course of 6 months, irrespective of the initial EF or revascularization success.     

Connective tissue components in serum in multiple myeloma: Analyses of propeptides of type I and type III procollagens,type I collagen telopeptide,and hyaluronan

The present study was performed to evaluate whether information concerning synthesis and degradation of type I collagen in multiple myeloma (MM) as obtained by serum analyses of C-terminal propeptide of type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) may be useful in evaluating the development of osteolytic bone destruction. Serum N-terminal propeptide of type III procollagen (PIIINP) may give information about marrow fibrosis in MM. No data are available about MM and serum hyaluronan, another important component of bone marrow stroma. We examined 15 consecutive patients before treatment and 15 sex- and age-matched controls. We found highly significant elevations in serum ICTP (median 6.2 vs. 2.4 μg/L; P < 0.01), PIIINP (median 5.2 vs. 2.9 μ/L; P < 0.01) and hyaluronan (median 122 vs. 45 μ/L; P < 0.01). ICTP in serum correlated closely to bone morbidity (r = 0.69; P < 0.01). Furthermore, serum ICTP correlated highly significantly to serum PIIINP (P < 0.01) and serum β₂-microglobulin (P < 0.01), whereas there was no correlation between hyaluronan and any of the collagen-derived peptides or β₂-microglobulin. The MM group was followed for 9–25 months and analysis of survival data suggested that serum ICTP may be of predictive value (P < 0.05). We conclude that important changes in connective tissue metabolism occur in MM. ICTP in serum seems to be a noninvasive marker of bone morbidity and may be of prognostic value. Furthermore, elevation of hyaluronan in serum is common in MM, the significance of which is unknown. © 1994 Wiley-Liss, Inc.     

Pulmonary capillary endothelial dysfunction in early systemic sclerosis

OBJECTIVE: Pulmonary capillary endothelium-bound angiotensin-converting enzyme (PCEB-ACE) activity is a sensitive and quantifiable index of endothelial function in vivo. Systemic sclerosis (SSc) is characterized by endothelial damage and excess collagen formation, causing mainly pulmonary hypertension (PH) in the limited cutaneous SSc (lcSSc) subset and interstitial lung disease with pulmonary interstitial fibrosis (PIF) in the diffuse cutaneous SSc (dcSSc) subset. This study was undertaken to investigate the hypothesis that PCEB-ACE activity is reduced early in SSc, in the absence of PH or PIF. METHODS: Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis and percent metabolism (%M) of a synthetic ACE substrate and calculated functional capillary surface area (FCSA) in 25 SSc patients and 11 controls. Substrate hydrolysis and %M reflect ACE activity per capillary; FCSA reflects ACE activity per vascular bed. RESULTS: PCEB-ACE activity was decreased in both SSc subsets. Among patients without PH, substrate hydrolysis and %M were decreased in patients with lcSSc and more profoundly in those with dcSSc; loss of FCSA normalized to body surface area (FCSA/BSA) was observed in dcSSc, but not in lcSSc. High-resolution computed tomography of the lung, performed in all SSc patients, revealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the degree of PIF; 5 dcSSc and 5 lcSSc patients with no detectable PIF exhibited decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcSSc. CONCLUSION: Depression of PCEB-ACE activity, indicating pulmonary endothelial dysfunction, occurs early in SSc, in the absence of PH or PIF, and is more pronounced, at this early pulmonary disease stage, in dcSSc than in lcSSc.