scholarly journals Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1295
Author(s):  
Paweł Rubiś ◽  
Ewa Dziewięcka ◽  
Magdalena Szymańska ◽  
Robert Banyś ◽  
Małgorzata Urbańczyk-Zawadzka ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Dilated Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Troponin T ◽  
Interstitial Fibrosis ◽  
Plasma Concentrations ◽  
Extracellular Volume ◽  
Type I ◽  
Replacement Fibrosis

The relationship between circulating fibrosis-related molecules and magnetic resonance-assessed cardiac fibrosis in dilated cardiomyopathy (DCM) is poorly understood. To compare circulating biomarkers between DCM patients with high and low fibrosis burdens, we performed a prospective, single-center, observational study. The study population was composed of 100 DCM patients (87 male, mean age 45.2 ± 11.8 years, mean ejection fraction 29.7% ± 10.1%). Replacement fibrosis was quantified by means of late gadolinium enhancement (LGE), whereas interstitial fibrosis was assessed via extracellular volume (ECV). Plasma concentrations of cardiotrophin-1, growth differentiation factor-15, platelet-derived growth factor, procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, and C-terminal telopeptide of type I collagen were measured. There were 44% patients with LGE and the median ECV was 27.7%. None of analyzed fibrosis serum biomarkers were associated with the LGE or ECV, whereas NT-proBNP was independently associated with both LGE and ECV, and troponin T was associated with ECV. None of the circulating fibrosis markers differentiated between DCM patients with and without replacement fibrosis, or patients stratified according to median ECV. However, cardiac-specific markers, such as NT-proBNP and hs-TnT, were associated with fibrosis. Levels of circulating markers of fibrosis seem to have no utility in the diagnosis and monitoring of cardiac fibrosis in DCM.

scholarly journals Extracellular volume is an independent predictor of arrhythmic burden in dilated cardiomyopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pawel P. Rubiś ◽  
Ewa M. Dziewięcka ◽  
Paweł Banyś ◽  
Małgorzata Urbańczyk-Zawadzka ◽  
Maciej Krupiński ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Independent Predictor ◽  
Interstitial Fibrosis ◽  
Extracellular Volume ◽  
Left Ventricular ◽  
Similar Distribution ◽  
Replacement Fibrosis ◽  
Decision Making Processes ◽  
Study Population

AbstractThe current stratification of arrhythmic risk in dilated cardiomyopathy (DCM) is sub-optimal. Cardiac fibrosis is involved in the pathology of arrhythmias; however, the relationship between cardiovascular magnetic resonance (CMR) derived extracellular volume (ECV) and arrhythmic burden (AB) in DCM is unknown. This study sought to evaluate the presence and extent of replacement and interstitial fibrosis in DCM and to compare the degree of fibrosis between DCM patients with and without AB. This is a prospective, single-center, observational study. Between May 2019 and September 2020, 102 DCM patients underwent CMR T1 mapping. 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) composed study population. AB was defined as the presence of VT or a high burden of PVCs. There were 41 (41.4%) patients with AB and 58 (58.6%) without AB. Replacement fibrosis was assessed with late gadolinium enhancement (LGE), whereas interstitial fibrosis with ECV. Overall, LGE was identified in 41% of patients. There was a similar distribution of LGE (without AB 50% vs. with AB 53.7%; p = 0.8) and LGE extent (without AB 4.36 ± 5.77% vs. with AB 4.68 ± 3.98%; p = 0.27) in both groups. ECV at nearly all myocardial segments and a global ECV were higher in patients with AB (global ECV: 27.9 ± 4.9 vs. 30.3 ± 4.2; p < 0.02). Only indexed left ventricular end-diastolic diameter (HR 1.1, 95%CI 1.0–1.2; p < 0.02) and global ECV (HR 1.12, 95%CI 1.0–1.25; p < 0.02) were independently associated with AB. The global ECV cut-off value of 31.05% differentiated both groups (AUC 0.713; 95%CI 0.598–0.827; p < 0.001). Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification of DCM patients into low or high AB. Interstitial fibrosis, expressed as ECV, was an independent predictor of AB in DCM. Incorporation of CMR parametric indices into decision-making processes may improve arrhythmic risk stratification in DCM.

scholarly journals Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thiago Ferreira de Souza ◽  
Thiago Quinaglia Silva ◽  
Lígia Antunes-Correa ◽  
Zsofia D. Drobni ◽  
Felipe Osório Costa ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Right Ventricular ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Extracellular Volume ◽  
Increased Risk ◽  
Tissue Characteristics ◽  
A Prospective Study

AbstractThere are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310–517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = −0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

scholarly journals The AP-1 Transcription Factor Fosl-2 Regulates Autophagy in Cardiac Fibroblasts during Myocardial Fibrogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 1861
Author(s):  
Jemima Seidenberg ◽  
Mara Stellato ◽  
Amela Hukara ◽  
Burkhard Ludewig ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Beclin 1 ◽  
Type I ◽  
Alpha Smooth Muscle Actin

Background: Pathological activation of cardiac fibroblasts is a key step in development and progression of cardiac fibrosis and heart failure. This process has been associated with enhanced autophagocytosis, but molecular mechanisms remain largely unknown. Methods and Results: Immunohistochemical analysis of endomyocardial biopsies showed increased activation of autophagy in fibrotic hearts of patients with inflammatory cardiomyopathy. In vitro experiments using mouse and human cardiac fibroblasts confirmed that blockade of autophagy with Bafilomycin A1 inhibited fibroblast-to-myofibroblast transition induced by transforming growth factor (TGF)-β. Next, we observed that cardiac fibroblasts obtained from mice overexpressing transcription factor Fos-related antigen 2 (Fosl-2tg) expressed elevated protein levels of autophagy markers: the lipid modified form of microtubule-associated protein 1A/1B-light chain 3B (LC3BII), Beclin-1 and autophagy related 5 (Atg5). In complementary experiments, silencing of Fosl-2 with antisense GapmeR oligonucleotides suppressed production of type I collagen, myofibroblast marker alpha smooth muscle actin and autophagy marker Beclin-1 in cardiac fibroblasts. On the other hand, silencing of either LC3B or Beclin-1 reduced Fosl-2 levels in TGF-β-activated, but not in unstimulated cells. Using a cardiac hypertrophy model induced by continuous infusion of angiotensin II with osmotic minipumps, we confirmed that mice lacking either Fosl-2 (Ccl19CreFosl2flox/flox) or Atg5 (Ccl19CreAtg5flox/flox) in stromal cells were protected from cardiac fibrosis. Conclusion: Our findings demonstrate that Fosl-2 regulates autophagocytosis and the TGF-β-Fosl-2-autophagy axis controls differentiation of cardiac fibroblasts. These data provide a new insight for the development of pharmaceutical targets in cardiac fibrosis.

Abstract 14664: Reduced Activin Like Kinase 1 Activity Promotes Cardiac Fibrosis in Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kevin Morine ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Emily Mackey ◽  
Mark Aronovitz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Left Ventricular ◽  
Lv Function ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels

Introduction: Activin receptor like kinase 1 (ALK1) mediates signaling via transforming growth factor beta-1 (TGFb1), a pro-fibrogenic cytokine. No studies have defined a role for ALK1 in heart failure. We tested the hypothesis that reduced ALK1 expression promotes maladaptive cardiac remodeling in heart failure. Methods and Results: ALK1 mRNA expression was quantified by RT-PCR in left ventricular (LV) tissue from patients with end-stage heart failure and compared to control LV tissue obtained from the National Disease Research Interchange (n=8/group). Compared to controls, LV ALK1 mRNA levels were reduced by 85% in patients with heart failure. Next, using an siRNA approach, we tested whether reduced ALK1 levels promote TGFb1-mediated collagen production in human cardiac fibroblasts. Treatment with an ALK1 siRNA reduced ALK1 mRNA levels by 75%. Compared to control, TGFb1-mediated Type I collagen and pSmad-3 protein levels were 2.5-fold and 1.7-fold higher, respectively, after ALK1 depletion. To explore a role for ALK1 in heart failure, ALK1 haploinsufficient (ALK1) and wild-type mice (WT; n=8/group) were studied 2 weeks after thoracic aortic constriction (TAC). Compared to WT, baseline LV ALK1 mRNA levels were 50% lower in ALK1 mice. Both LV and lung weights were higher in ALK1 mice after TAC. Cardiomyocyte area and LV mRNA levels of BNP, RCAN, and b-MHC were increased similarly, while SERCa levels were reduced in both ALK1 and WT mice after TAC. Compared to WT, LV fibrosis (Figure) and Type 1 Collagen mRNA and protein levels were higher among ALK1 mice. Compared to WT, LV fractional shortening (48±12 vs 26±10%, p=0.01) and survival (Figure) were lower in ALK1 mice after TAC. Conclusions: Reduced LV expression of ALK1 is associated with advanced heart failure in humans and promotes early mortality, impaired LV function, and cardiac fibrosis in a murine model of heart failure. Further studies examining the role of ALK1 and ALK1 inhibitors on cardiac remodeling are required.

scholarly journals Activated myofibroblasts promote cardiac hypertrophy and systolic dysfunction independently of cardiac fibrosis in experimental autoimmune myocarditis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Tkacz ◽  
A Jazwa-Kusior ◽  
F Rolski ◽  
E Dzialo ◽  
K Weglarczyk ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Dilated Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Systolic Dysfunction ◽  
Heart Weight ◽  
Type I ◽  
Autoimmune Myocarditis ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Abstract Background/Introduction Heart-specific inflammation – myocarditis is a common cause dilated cardiomyopathy which is characterized by pathological tissue remodeling, ventricular stiffening, cardiomyopathy and heart failure. In experimental autoimmune myocarditis (EAM) susceptible mice immunized with alpha myosin heavy chain (αMyHC) and complete Freund's adjuvant (CFA) develop acute myocarditis driven by autoreactive CD4+ T cells that is followed by progressive fibrosis, cardiomyopathy and systolic dysfunction. Purpose The aim of the study was to investigate the role of cardiac fibroblasts and myofibroblasts in myocarditis and post-inflammatory dilated cardiomyopathy in mouse model of EAM. Methods EAM was induced in BALB/c mice by immunization with αMyHC/CFA. We used reporter mice expressing EGFP under collagen type I promoter (Coll-EGFP) and RFP under a control of α-smooth muscle actin (αSMA) promoter (αSMA-RFP) and transgenic αSMA-TK mice with ganciclovir-inducible ablation of proliferating myofibroblasts. Cardiac cells were quantified using flow cytometry. Cardiac fibroblasts (CD45-CD31-EGFP+) were sorted from healthy and myocarditis-positive (day 21) mice using BD FACSAria™ II Cell Sorter and analyzed for the whole genome transcriptomics by RNA sequencing. Echocardiography was performed on Vevo 2100 Imaging System. Cardiac fibrosis was assessed by Trichrome Massons's staining and hydroxyproline assay, whereas cardiac hypertrophy by analysing cross-sectional cardiomyocyte area. Profibrotic gene expression was assessed by qRT-PCR. Results The total number of cardiac fibroblasts (CD45-CD31-EGFP+) and the subset of myofibroblasts (CD45-CD31-EGFP+RFP+) remained unchanged at inflammatory (d21) and fibrotic stages (d40). Analysis of differentially expressed genes (min. 2x fold change, p value &lt;0.05) pointed out activation of immune processes (mainly chemokine production), response to stress, cytoskeletal and extracellular matrix re-organization in cardiac fibroblasts in response to myocarditis. αSMA-TK mice treated with ganciclovir (from day 21) showed comparable percent of fibrotic area, but significantly reduced heart weight, decreased cardiomyocyte hypertrophy and improved ejection fraction and cardiac output at day 40 comparing to PBS-treated mice. Ganciclovir-treated mice showed also attenuated cardiac Acta2 and Srf but markedly enhanced Mmp2 expression. Conclusions In EAM model cardiac fibroblasts actively participate in proinflammatory and profibrotic responses, while activated myofibroblasts contribute to dilated cardiomyopathy development independently of cardiac fibrosis. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre (Poland)

Type VI collagen induces cardiac myofibroblast differentiation: implications for postinfarction remodeling

2006 ◽  
Vol 290 (1) ◽  
pp. H323-H330 ◽  
Author(s):  
Jennifer E. Naugle ◽  
Erik R. Olson ◽  
Xiaojin Zhang ◽  
Sharon E. Mase ◽  
Charles F. Pilati ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
In Vivo Model ◽  
Type Iii Collagen ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Type Vi Collagen ◽  
Collagen Substrate ◽  
Type Iii

Cardiac fibroblast (CF) proliferation and differentiation into hypersecretory myofibroblasts can lead to excessive extracellular matrix (ECM) production and cardiac fibrosis. In turn, the ECM produced can potentially activate CFs via distinct feedback mechanisms. To assess how specific ECM components influence CF activation, isolated CFs were plated on specific collagen substrates (type I, III, and VI collagens) before functional assays were carried out. The type VI collagen substrate potently induced myofibroblast differentiation but had little effect on CF proliferation. Conversely, the type I and III collagen substrates did not affect differentiation but caused significant induction of proliferation (type I, 240.7 ± 10.3%, and type III, 271.7 ± 21.8% of basal). Type I collagen activated ERK1/2, whereas type III collagen did not. Treatment of CFs with angiotensin II, a potent mitogen of CFs, enhanced the growth observed on types I and III collagen but not on the type VI collagen substrate. Using an in vivo model of myocardial infarction (MI), we measured changes in type VI collagen expression and myofibroblast differentiation after post-MI remodeling. Concurrent elevations in type VI collagen and myofibroblast content were evident in the infarcted myocardium 20-wk post-MI. Overall, types I and III collagen stimulate CF proliferation, whereas type VI collagen plays a potentially novel role in cardiac remodeling through facilitation of myofibroblast differentiation.

Relationship between cardiac magnetic resonance derived extracellular volume fraction and myocardial strain in patients with non-ischemic dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Azuma ◽  
S Kato ◽  
S Kodama ◽  
K Hayakawa ◽  
M Kagimoto ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Dilated Cardiomyopathy ◽  
Myocardial Fibrosis ◽  
Negative Correlation ◽  
T1 Mapping ◽  
Myocardial Strain ◽  
Extracellular Volume ◽  
P Values ◽  
Chamber View ◽  
Non Ischemic Dilated Cardiomyopathy

Abstract Background The feature tracking (FT) technique has been proposed as a robust method to evaluate the myocardial strain using conventional cine magnetic resonance imaging (MRI) of the left ventricle. Data is limited regarding the relationship between FT-derived myocardial strain and diffuse myocardial fibrosis evaluated by T1 mapping in patients with non-ischemic dilated cardiomyopathy (NIDCM). Purpose The aim of this study was to evaluate the correlation between extracellular volume (ECV) by T1 mapping and myocardial strain by FT in patients with NIDCM. Methods A total of sixty-four patients with NIDCM (62±12 years) and 15 controls (62±11 years) were studied. Using a 1.5T MR scanner, pre- and post- T1 mapping images of LV wall at mid-ventricular level was acquired to calculate ECV by modified Look-Locker inversion recovery (MOLLI) sequence. Radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) was assessed by FT technique. ECV and myocardial strain were compared using a 6-segment model at mid-ventricular level. Results Compared to the controls, the NIDCM patients had a significantly higher ECV (0.30±0.02 vs. 0.24±0.01, p&lt;0.001) and impaired myocardial strain (RS, 24.2±3.0 vs. 52.2±6.2, p&lt;0.001; CS, −7.5±2.1 vs. −15.3±2.2, p&lt;0.001; LS −10.4±3.5 vs. −20.2±4.7, p&lt;0.001, respectively). Similar results were obtained when comparing all 6 myocardial segments (segment 7–12) (all p values &lt;0.001). In a segment-based analysis, a significant positive correlation was found between the ECV and CS (r=0.26 to 0.41; all p values &lt;0.05), a negative correlation was found between the ECV and RS (r=−0.31 to −0.41; all p values &lt;0.05). In a patient-based analysis, there were significant positive correlations between the ECV and CS (r=0.45, p&lt;0.001), ECV and LS from 2-chamber view (r=0.30, p=0.006), ECV and LS from 4-chamber view (r=0.37, p&lt;0.001). There was a significant negative correlation between the ECV and RS (r=−0.43, p&lt;0.001) (FIGURE) Conclusions In NIDCM patients, severity of myocardial fibrosis evaluated by T1 mapping is associated with impaired myocardial strain by FT technique. Correlation between the ECV and strain Funding Acknowledgement Type of funding source: None

scholarly journals Severely restricting energy intake for 24 h does not affect markers of bone metabolism at rest or in response to re-feeding

2020 ◽  
Vol 59 (8) ◽  
pp. 3527-3535
Author(s):  
David J. Clayton ◽  
Lewis J. James ◽  
Craig Sale ◽  
Iain Templeman ◽  
James A. Betts ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Energy Intake ◽  
Type I Collagen ◽  
Plasma Concentrations ◽  
Energy Restriction ◽  
Type I ◽  
Procollagen Type ◽  
Markers Of Bone Turnover ◽  
Ad Libitum

Abstract Purpose Intermittent energy restriction commonly refers to ad libitum energy intake punctuated with 24 h periods of severe energy restriction. This can improve markers of metabolic health but the effects on bone metabolism are unknown. This study assessed how 24 h severe energy restriction and subsequent refeeding affected markers of bone turnover. Methods In a randomised order, 16 lean men and women completed 2, 48 h trials over 3 days. On day 1, participants consumed a 24 h diet providing 100% [EB: 9.27 (1.43) MJ] or 25% [ER: 2.33 (0.34) MJ] of estimated energy requirements. On day 2, participants consumed a standardised breakfast (08:00), followed by an ad libitum lunch (12:00) and dinner (19:30). Participants then fasted overnight, returning on day 3. Plasma concentrations of C-terminal telopeptide of type I collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and parathyroid hormone (PTH) were assessed as indices of bone metabolism after an overnight fast on days 1–3, and for 4 h after breakfast on day 2. Results There were no differences between trials in fasting concentrations of CTX, P1NP or PTH on days 1–3 (P > 0.512). During both trials, consuming breakfast reduced CTX between 1 and 4 h (P < 0.001) and PTH between 1 and 2 h (P < 0.05), but did not affect P1NP (P = 0.773) Postprandial responses for CTX (P = 0.157), P1NP (P = 0.148) and PTH (P = 0.575) were not different between trials. Ad libitum energy intake on day 2 was greater on ER [12.62 (2.46) MJ] than EB [11.91 (2.49) MJ]. Conclusions Twenty-four hour severe energy restriction does not affect markers of bone metabolism.

scholarly journals High doses of TGF-β potently suppress type I collagen via the transcription factor CUX1

2011 ◽  
Vol 22 (11) ◽  
pp. 1836-1844 ◽  
Author(s):  
Maria Fragiadaki ◽  
Tetsurou Ikeda ◽  
Abigail Witherden ◽  
Roger M Mason ◽  
David Abraham ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Aberrant Expression

Transforming growth factor-β (TGF-β) is an inducer of type I collagen, and uncontrolled collagen production leads to tissue scarring and organ failure. Here we hypothesize that uncovering a molecular mechanism that enables us to switch off type I collagen may prove beneficial in treating fibrosis. For the first time, to our knowledge, we provide evidence that CUX1 acts as a negative regulator of TGF-β and potent inhibitor of type I collagen transcription. We show that CUX1, a CCAAT displacement protein, is associated with reduced expression of type I collagen both in vivo and in vitro. We show that enhancing the expression of CUX1 results in effective suppression of type I collagen. We demonstrate that the mechanism by which CUX1 suppresses type I collagen is through interfering with gene transcription. In addition, using an in vivo murine model of aristolochic acid (AA)-induced interstitial fibrosis and human AA nephropathy, we observe that CUX1 expression was significantly reduced in fibrotic tissue when compared to control samples. Moreover, silencing of CUX1 in fibroblasts from kidneys of patients with renal fibrosis resulted in increased type I collagen expression. Furthermore, the abnormal CUX1 expression was restored by addition of TGF-β via the p38 mitogen-activated protein kinase pathway. Collectively, our study demonstrates that modifications of CUX1 expression lead to aberrant expression of type I collagen, which may provide a molecular basis for fibrogenesis.

Abstract 14244: Gender-Specific Association Between Serum Markers of Systemic Inflammation and Interstitial Cardiac Fibrosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Victor Nauffal ◽  
Bharath Ambale Venkatesh ◽  
Colin Wu ◽  
Hossein Bahrami ◽  
Russell Tracy ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
T1 Mapping ◽  
Cardiac Fibrosis ◽  
Ventricular Remodeling ◽  
Volume Fraction ◽  
Interstitial Fibrosis ◽  
Extracellular Volume ◽  
Inverse Association ◽  
Post Contrast ◽  
Markers Of Inflammation

Introduction: Inflammation contributes to pathogenic ventricular remodeling. Recently, T1 mapping has been used to non-invasively measure interstitial myocardial fibrosis. We examined the association between baseline markers of systemic inflammation and interstitial fibrosis measured using T1 mapping at 10 years follow-up in MESA. Methods and Results: 1,156 participants underwent cardiac magnetic resonance imaging with T1 mapping. All analyses were stratified by gender. Three hierarchical multivariable linear regression models were constructed to assess the risk-adjusted association of baseline C-reactive protein (CRP), interleukin 6 (IL-6) and fibrinogen with 25 minutes post-contrast myocardial T1 time (T1Myo25). Shorter T1Myo25 reflect increasing levels of interstitial fibrosis. We found a non-linear relationship between IL-6 and T1Myo25 in males (Figure 1A). A significant negative association between T1Myo25 and increasing levels of IL-6 was found in males that reversed at IL-6 levels ≥2.7pg/ml. Moreover in males, increasing levels of fibrinogen were significantly negatively associated with T1Myo25, while a similar but non-significant trend was found for CRP (Figure 1B). In women, there was a similar inverse association between T1Myo25 and increasing levels of all three markers of systemic inflammation prior to adjusting for body mass index that became statistically non-significant following adjustment (Figure 1B). Similar associations with markers of inflammation were found using extracellular volume fraction and T1Myo12 as measures of interstitial fibrosis. Conclusions: Markers of systemic inflammation in males, particularly IL-6 and fibrinogen, are independently associated with increased interstitial fibrosis. In females, this association may be mediated by the obesity-induced inflammatory-state. These findings highlight the early role of inflammation in the pathogenesis of heart failure.

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