Collagen Volume Fraction Research Articles

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study.

Myocardial fibrosis in aortic stenosis is associated with worse survival following aortic valve replacement. We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. A total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement and T1 mapping and global longitudinal strain analysis. Collagen volume fraction was measured in myocardial biopsies (71) that were sampled at the time of AVR. Results. CVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19–33) vs 20.7% (15–30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=−0.303, p=0.013) and non-invasively (native T1; r=−0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. Conclusion. Our data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

Novel oral edaravone attenuates diastolic dysfunction of diabetic cardiomyopathy by activating the Nrf2 signaling pathway

Oxidative stress plays a crucial role in the pathophysiology of diastolic dysfunction associated with diabetic cardiomyopathy. Novel oral edaravone (OED) alleviates oxidative stress by scavenging free radicals and may be suitable for the treatment of chronic diseases such as diabetic cardiomyopathy. Oral administration of OED to type 2 diabetic rats (induced by high-sugar/high-fat diet and intraperitoneal injection of streptozotocin) for 4 w decreased malondialdehyde and increased superoxide dismutase. Moreover, it significantly improved ratios of early to late diastolic peak velocity, myocardium hypertrophy accompanied by decreased cross-sectional areas of cardiomyocytes, the proportion of apoptotic cells, collagen volume fractions, and deposition of collagen I/III. In H9c2 cells, OED reduced reactive oxygen species, cell surface area, and numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells induced by glucolipotoxicity. OED remarkably upregulated expression of the nuclear factor E2-related factor (Nrf2) signaling pathway both in vivo and in vitro. In addition, OED promoted Nrf2 nuclear translocation and upregulated nicotinamide adenine dinucleotide phosphate quinone oxidoreductase and heme oxygenase. Silencing of Nrf2 abolished the protective effect of OED in H9c2 cells. Our findings demonstrate that OED has the therapeutic potential to ameliorate diastolic dysfunction associated with diabetic cardiomyopathy. Its effect was mainly achieved by attenuating hyperglycemia and hyperlipidemia-induced cardiomyocyte hypertrophy, apoptosis, and fibrosis by activating the Nrf2 signaling pathway.

Grape seed proanthocyanidin alleviates left ventricular remodeling by regulating systolic pressure, oxidative stress and vasoactive substances in spontaneously hypertensive rats

Purpose: To study the effect of grape seed proanthocyanidin (GSP) on left ventricular remodeling in spontaneously hypertensive rats, and the underlying mechanism.&#x0D; Methods: Spontaneously hypertensive rats were randomly divided into two groups, with 12 rats per group. One group was injected with GSP. Systolic pressure in each group was measured at baseline (before treatment), and at 3, 6 and 9 weeks after treatment. Whole heart index and left heart index were calculated. Histopathological changes in myocardium and left ventricular posterior wall thickness of rats in each group were measured. The cross-sectional area of myocardial cells and myocardial collagen volume fraction were assessed. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO), renin, angiotensin II (Ang II), endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) in each group of rats were assayed.&#x0D; Results: Compared with the spontaneous hypertension group, whole heart mass index, left heart mass index, left ventricular posterior wall thickness, cross sectional area of myocardial cells, myocardial collagen volume fraction, and levels of MDA, renin, Ang II and ET-1 in GSP group were significantly decreased, while the expression levels of SOD, CAT, NO and eNOS were markedly increased in GSP group (p &lt; 0.05). Cell hypertrophy in the GSP group was significantly mitigated, when compared with that in the spontaneous hypertension group.&#x0D; Conclusion: GSP mitigates left ventricular remodeling in rats by reducing systolic blood pressure, improving antioxidant capacity and regulating levels of vasoactive substances, thus suggesting its potential for the management of hypertension.

Diabetes and Myocardial Fibrosis: A Systematic Review and Meta-Analysis

ObjectivesThis systematic review and meta-analysis investigated the association of diabetes and glycemic control with myocardial fibrosis (MF). BackgroundMF is associated with an increased risk of heart failure, coronary artery disease, arrhythmias, and death. Diabetes may influence the development of MF, but evidence is inconsistent. MethodsThe authors searched EMBASE, Medline Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar for observational and interventional studies investigating the association of diabetes, glycemic control, and antidiabetic medication with MF assessed by histology and cardiac magnetic resonance (ie, extracellular volume fraction [ECV%] and T1 time). ResultsA total of 32 studies (88% exclusively on type 2 diabetes) involving 5,053 participants were included in the systematic review. Meta-analyses showed that diabetes was associated with a higher degree of MF assessed by histological collagen volume fraction (n = 6 studies; mean difference: 5.80; 95% CI: 2.00-9.59) and ECV% (13 studies; mean difference: 2.09; 95% CI: 0.92-3.27), but not by native or postcontrast T1 time. Higher glycosylated hemoglobin levels were associated with higher degrees of MF. ConclusionsDiabetes is associated with higher degree of MF assessed by histology and ECV% but not by T1 time. In patients with diabetes, worse glycemic control was associated with higher MF degrees. These findings mostly apply to type 2 diabetes and warrant further investigation into whether these associations are causal and which medications could attenuate MF in patients with diabetes.

Identifying early stages of doxorubicin-induced cardiotoxicity in rat model by 7.0 tesla cardiovascular magnetic resonance combining hematological and pathological parameters

PurposeTo identify early doxorubicin-induced cardiotoxicity by applying 7.0 T cardiac magnetic resonance (CMR) combined with creatine kinase isoenzymes (CKMB) from rat models, using pathological results as a reference standard. MethodsThe 48 male rats included in the study were divided into a doxorubicin (DOX) group (n = 32) and a control group (n = 16). Each group was further divided into four subgroups according to the interval weeks between the first administration and CMR examination. DOX group and the controls were injected with DOX (2.5 mg/kg) or physiological saline (2.5 mg/kg) through vena caudalis weekly. The rats in first subgroup received 4 weekly injections and were sacrificed after CMR examination at week 4. Rats in the second, third and fourth DOX or control subgroups underwent 6 weekly injections and were sacrificed after CMR examination at weeks 6, 8 and 10, respectively. The conventional cardiac function parameters, myocardial strain, standardized myocardial T2 value, late gadolinium enhancement, CKMB and pathological results of each rat were analyzed. ResultsThe LV mass index was reduced and CKMB was increased in the first subgroup (week 4), global circumference strain was decreased and normalized myocardial T2 relaxation time was prolonged in the second subgroup (week 6). At these early point of time, LVEF remained unaffected. Myocardial fibrosis was observed in the third and fourth subgroups (in week 8 and 10, respectively) and the collagen volume fraction was significantly negatively correlated with the LVEF and myocardial strain. ConclusionsCMR can be used to identify doxorubicin-induced cardiotoxicity at early stage, with the LV mass index, global circumference strain, normalized myocardial T2 relaxation time as the early markers. CKMB can indicate the optimal timing for CMR examination of chemotherapy recipients to improve medical efficiency. Myocardial fibrosis persists in the advanced stage of doxorubicin-induced cardiotoxicity which comprises the main cause of LV dysfunction.

Serum autotaxin as a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy.

AimsAutotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non‐ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM.Methods and resultsWe enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high‐ATX group and low‐ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6–689.5) pg/mL vs. 96.5 (40.8–191.5) pg/mL, P = 0.010] were higher in the high‐ATX group than low‐ATX group, whereas high‐sensitivity C‐reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan–Meier survival analysis revealed that the event‐free survival rate was significantly lower in the high‐ATX group than low‐ATX group (log‐rank; P = 0.007). Cox proportional hazard analysis revealed that high‐ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high‐sensitivity C‐reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048).ConclusionHigh serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

Investigation of Left Ventricular Strain and Its Morphological Basis During Different Stages of Diastolic and Systolic Dysfunction in Spontaneously Hypertensive Rat.

Myocardial fibrosis plays an important role in the pathogenesis of hypertensive cardiac dysfunction, and myocardial strain could detect early systolic abnormalities when left ventricular ejection fraction (LVEF) is preserved. The aim of this study was to investigate the characteristics of left ventricular multidirectional strain during different stages of heart dysfunction and the possible morphological basis in spontaneously hypertensive rats (SHRs). SHRs and Wistar-Kyoto (WKY) rats were randomly divided into cages and observed for 3-25 months. Echocardiographic measurements, LV + dp/dtmax and left ventricular end-diastolic pressure (LVEDP), and histological collagen volume fraction (CVF) were observed in all rats. According to LVEF and LVEDP, SHRs were divided into normal cardiac function group (group A), diastolic dysfunction group (group B1), and systolic dysfunction group (group B2). In group A, myocardial strain and CVF showed no difference compared with the control group. In group B1, global longitudinal strain (GLS) and endocardial longitudinal strain (SL-endo) were lower than those in group A CVF-endo was increased (all P < 0.05). In group B2, global and layer-specific strain decreased significantly, along with the increased CVF-endo and CVF-epi (all P < 0.05). The decrease of GLS and SL-endo was moderately correlated with the increase of CVF-endo. The reduction of LVEF was correlated with the decrease of SC-endo (r = 0.65, P < 0.01). Pathological myocardial fibrosis associated with hypertension develops from the inner to outer layer of myocardium, which is coincident with the impairment of myocardial deformation, where longitudinal strain is involved firstly and LVEF declines when all directions of strain are reduced.

Phenotypic characterization of primary cardiac fibroblasts from patients with HFpEF.

Heart failure is a leading cause of hospitalizations and mortality worldwide. Heart failure with a preserved ejection fraction (HFpEF) represents a significant clinical challenge due to the lack of available treatment modalities for patients diagnosed with HFpEF. One symptom of HFpEF is impaired diastolic function that is associated with increases in left ventricular stiffness. Increases in myocardial fibrillar collagen content is one factor contributing to increases in myocardial stiffness. Cardiac fibroblasts are the primary cell type that produce fibrillar collagen in the heart. However, relatively little is known regarding phenotypic changes in cardiac fibroblasts in HFpEF myocardium. In the current study, cardiac fibroblasts were established from left ventricular epicardial biopsies obtained from patients undergoing cardiovascular interventions and divided into three categories: Referent control, hypertension without a heart failure designation (HTN (-) HFpEF), and hypertension with heart failure (HTN (+) HFpEF). Biopsies were evaluated for cardiac myocyte cross-sectional area (CSA) and collagen volume fraction. Primary fibroblast cultures were assessed for differences in proliferation and protein expression of collagen I, Membrane Type 1-Matrix Metalloproteinase (MT1-MMP), and α smooth muscle actin (αSMA). Biopsies from HTN (-) HFpEF and HTN (+) HFpEF exhibited increases in myocyte CSA over referent control although only HTN (+) HFpEF exhibited significant increases in fibrillar collagen content. No significant changes in proliferation or αSMA was detected in HTN (-) HFpEF or HTN (+) HFpEF cultures versus referent control. Significant increases in production of collagen I was detected in HF (-) HFpEF fibroblasts, whereas significant decreases in MT1-MMP levels were measured in HTN (+) HFpEF cells. We conclude that epicardial biopsies provide a viable source for primary fibroblast cultures and that phenotypic differences are demonstrated by HTN (-) HFpEF and HTN (+) HFpEF cells versus referent control.

Coprinus comatus polysaccharides ameliorated carbon tetrachloride-induced liver fibrosis through modulating inflammation and apoptosis.

Liver fibrosis is a serious global public health problem, owing to a lack of effective treatment. Coprinus comatus polysaccharides (CP), isolated from C. comatus, possess multiple biological activities. In our work, water-soluble polysaccharides (CPa) from CP were obtained by column chromatography. We attempted to investigate the anti-liver fibrosis ability of CPa and the underlying mechanisms of its activity against liver fibrosis in vivo and in vitro, as well as its structure. In vivo results showed that CPa reduced the release of inflammatory factors and apoptosis by modulating the TLR4/MyD88/NF-κB, Bcl-2/Bax and caspase family signaling pathways, thereby attenuating serum enzymes, ROS, α-SMA, collagen III, TGFβ1, p-Smad3, and collagen volume fraction, and increasing the defense capacity of the antioxidant defense system in tetrachloride (CCl4)-induced liver fibrosis mice. The in vitro result was used to verify that, in vivo, CPa regulated the TLR4/MyD88/NF-κB, Bcl-2/Bax and caspase family signaling pathways to prevent the activation of HSCs and accelerate HSCs apoptosis in activated LX-2 cells. Thus, CPa could attenuate liver fibrosis by mediating inflammation and apoptosis. Meantime, the structural analysis showed that CPa is a polysaccharide with α- and β-configurations including Fuc, Man, Gal and Glc with a Mw of 524 kDa. These findings indicate that CPa could be developed into functional foods and drugs against liver fibrosis.

Platelet-Derived Growth Factor-A Overexpression Correlates with Atrial Fibrosis in the Patients with Atrial Fibrillation Secondary to Rheumatic Valvular Disease

Objective: To investigate the relationship between platelet-derived growth factor-A (PDGF-A) and atrial fibrosis in patients who have developed atrial fibrillation (AF) secondary to rheumatic valvular disease. Methods: 84 selected patients participated in the current study who have developed rheumatic heart disease and were going to have a cardiac surgical operation. In the current study, whole subjects were divided into two group, they were atrial fibrillation (AF) group (the quantity is thirty-nine) and sinus rhythm (SR) group (the quantity is forty-five). Before the operation, complete clinical data was available for the whole patients. During the operation, the right atrial tissue (0.3 - 0.5 mm3) was disserted from every patient. Right atrial fibrosis was observed by Masson staining and the distribution of PDGF-A in right atrium specimen was observed by immunohistochemistry. RT-PCR techniques were applied to admeasure the mRNA expressions of PDGF-A in patients’ atrial tissue. At the same time, western-Blot techniques were employed to admeasure the protein expressions of PDGF-A. Results: In baseline clinical characteristics, in both AF group and SR group, there was no apparently difference between them (P > 0.05); compared with SR group, the diameters of left atrium and right atrium in AF group were apparently increased (P < 0.05). The results of Masson staining revealed that the atrial tissue fibrosis was clearer in AF group, and collagen volume fraction in the AF group was evidently exceeding SR group (P < 0.05). The expressions of PDGF-A’s mRNA and protein from right atrial tissue in the AF group were evidently greater than SR group (P < 0.05). The mRNA and protein expressions of PDGF-A and the right atrium diameter go hand in hand. Conclusion: Atrial remodeling plays an important role in patients with valvular atrial fibrillation; PDGF-A in patients with AF was highly expressed in the right atrial, and was closely related with atrial fibrosis.

Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice.

PurposeThis study was designed to evaluate the effects of PD-1 inhibitor on lung tissue morphology and the immune system in a mouse model of radiation-induced lung injury (RILI) and to assess interactions between radiation therapy and PD-1 inhibition.MethodsTwenty C57BL/6 mice were divided randomly into four groups of five mice each. Mice were treated with an anti-mouse PD-1 monoclonal antibody, whole thorax irradiation, both or neither. Lung tissue morphology and pathological changes were assessed by hematoxylin-eosin staining; lung fibrosis was assessed by Masson staining and analysis of hydroxyproline; CD3+, CD4+, and CD8+ T lymphocytes in lung tissues were detected immunohistochemically; and the concentrations of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) in lung tissue were evaluated by cytokine multiplex analysis.ResultsLung injury scores and indicators of pulmonary fibrosis were higher in mice administration whole thorax irradiation than in control mice. Inflammatory infiltrate scores, alveoli deformation scores, collagen volume fractions and hydroxyproline contents in lung tissues were all significantly higher in mice administered PD-1 inhibitor plus irradiation than in the other three groups. Similarly, the percentages of CD3+ and CD8+T cells and the concentrations of IL-6 and TGF-β1 in lung tissue were significantly higher in mice treated with radiation and PD-1 inhibitor than in the other groups. However, PD-1 inhibitor and irradiation interacted significantly only in the elevation of TGF-β1 level.ConclusionWhole thorax X-ray irradiation in mice can cause pulmonary injury and fibrosis, which could be exacerbated by PD-1 inhibitors. Radiotherapy combined with PD-1 inhibitors may aggravate RILI by synergistically upregulating TGF-β1 expression, thereby affecting the immune-inflammatory microenvironment in the lungs.

The therapeutic effect and mechanism of Rapamycin combined with HO-3867 on monocrotaline-induced pulmonary hypertension in rats

This study test was designed to investigate the possible modulatory effect of rapamycin combined with HO-3867 in monocrotaline(MCT)-induced pulmonary arterial hypertension in rats. We hypothesized that combined treatment with rapamycin and HO-3867 is superior to either alone in attenuating MCT-induced rat pulmonary arterial hypertension (PAH). Pulmonary arterial hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). 2 weeks later, rapamycin (2 mg/kg i.p.) and HO3867 (10 mg/kg i.h.) were administered daily, alone and in combination, for 2 weeks. Right ventricular systolic pressure, echocardiography were recorded and then rats were sacrificed. Histological analysis of pulmonary arteries medial wall thickness, right ventricular hypertrophy index (RVHI), the ratio of right ventricular to body weight, and collagen volume fraction (CVF) of right ventricular were performed. Moreover, the expression of t-STAT3, p-STAT3, t-Akt, p-Akt in lung and t-STAT3, p-STAT3, t-S6, p-S6 in right ventricular were examined. The result showed that combined treatment provided a considerable improvement toward maintaining hemodynamic changes, lung vascular remodeling as well as amending RV remodeling and function. Furthermore, Combined treatment can normalize the protein levels of two signal pathways in lung and heart tissue, where p-S6 or p-Akt significantly decreased compared to HO-3867 alone, or p-STAT3 significantly reduced compared to rapamycin alone. In conclusion, combined treatment with rapamycin and HO-3867 is superior to either alone in attenuating MCT-induced PAH in rats.

Effects of myocardial fibrosis on ischemic preconditioning against myocardial ischemia-reperfusion injury in type 2 diabetic rats

Objective: To assess whether myocardial fibrosis affects the protective efficiency of ischemic preconditioning (IPC) against myocardial ischemia/reperfusion injury (MIRI) in type 2 diabetic rats. Methods: Type 2 diabetic rat model was established. Fifty-four normal and 54 diabetic spragus-dawley (SD) rats were equally divided into 6 groups (n=18) using the random number table method: (1) Control group (C group); (2) Ischemia reperfusion injury (IRI) control group (IRI group); (3) IPC group; (4) Diabetic control group (DC group); (5) Diabetic IRI group (DIRI group); (6) Diabetic IPC group (DIPC group). After the reperfusion, blood samples were obtained for measuring serum concentrations of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) using enzyme-linked immunosorbent assay (ELISA). The myocardial infarction size (IS) was assessed by double staining method with Evan's blue and Triphenyl tetrazolium chloride (TTC), and the myocardial collagen volume fraction (CVF) and perivascular collagen area (PVCA) were assessed by Masson staining. Results: A stable and effective rat model with long-term diabetes was established in the current study. Compared with the normal rat groups, the CVF and PVCA significantly increased (all P<0.05) in the diabetic rat groups. The levels of CK-MB, cTnI and IS in the IPC group were (6.6±0.8) ng/ml, (0.5±0.1) ng/ml and (25.1±4.7) %, which showed significant decrease compared with (12.3±1.1) ng/ml, (1.2±0.3) ng/ml and (52.3±8.1) % in IRI group (all P<0.05). Among the diabetic rat groups, the CK-MB and cTnI levels in DIPC group were (11.5±0.9) and (1.1±0.1) ng/ml, apparently lower than the levels of (16.6±2.2) and (1.4±0.3) ng/ml in the DIRI group (both P<0.05). Compared with the IPC group, the IS, CK-MB and cTnI levels significantly increased in the DIPC group (all P<0.05). Conclusion: Myocardial fibrosis exists in rats with long-term type 2 diabetes, which weakens the protective effect of IPC on diabetes MIRI.

Prognostic implications of fibrosis in low risk aortic stenosis patients

Introduction and objectivesAmong patients with aortic stenosis (AS), interstitial fibrosis has been associated with progression to heart failure and is a marker of poorer prognosis. We aimed to assess the impact of myocardial fibrosis on clinical events after aortic valve replacement (AVR) in low risk, severe AS. MethodsWe prospectively followed 56 severe AS patients with ejection fraction >40%, who underwent AVR with simultaneous myocardial biopsies and collagen volume fraction (CVF) determination. Baseline and follow-up echocardiographic parameters were assessed. Outcomes were all-cause death and the combined endpoint of all-cause death or non-fatal cardiovascular hospitalization. ResultsPatients were predominantly women (67.9%) and mean age was 66±12 years. At follow-up, there was a significant decrease in transaortic gradients and wall stress, as well as regression in indexed LV mass. Patients who suffered a fatal event or the combined endpoint had a higher degree of fibrosis (27.1±20.7% vs. 15.4±11.8%, p=0.035; 24.0±18.2% vs. 15.3±12.0%, p=0.038, respectively). Patients with CVF≥15.4% had higher rates of all-cause death (37.5% vs. 97.0%, p=0.001) and lower survival free of the combined endpoint of all-cause death or non-fatal cardiovascular hospitalization (0% vs. 91.2%, p<0.001). CVF was the only independent predictor of all-cause death (hazard ratio (HR) 1.88; 95% confidence interval (CI): 1.08-3.29 for each 10% increase; p=0.026) and all-cause death or cardiovascular hospitalization (HR 1.73; 95% CI: 1.03-2.911 for each 10% increase; p=0.038). ConclusionsIn low risk AS patients, higher levels of fibrosis are independent predictors of all-cause death and the composite of all-cause death or non-fatal cardiovascular hospitalization. Further advances in anti-fibrotic therapies in AS are needed.

Effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats

Effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats

Histologic validation of stress cardiac magnetic resonance T1-mapping techniques for detection of coronary microvascular dysfunction in rabbits

BackgroundTo investigate the diagnostic performance of stress cardiac magnetic resonance (CMR) T1-mapping for the detection of coronary microvascular dysfunction (CMD) by correlating microvascular density (MVD) and collagen volume fraction (CVF) with T1 response to adenosine triphosphate (ATP) stress (stress ΔT1) in rabbits. MethodsTwenty-four New Zealand white rabbits were randomly divided into the CMD group induced by microembolization spheres (n = 10), sham-operated group (n = 5), and control group (n = 9). All rabbits underwent 3.0 T CMR, both rest and ATP stress T1-maps were obtained, and first-pass perfusion imaging was performed. Stress ΔT1 and myocardial perfusion reserve index (MPRI) were calculated. For the histologic study, each rabbit was sacrificed after CMR scanning. Left ventricular myocardial tissue was stained with Hematoxylin-eosin (H&E), Masson, and CD31, from which MVD and CVF were extracted. Pearson correlation analyses were performed to determine the strength of the association between the stress ΔT1 and both MVD and CVF. ResultsThe stress ΔT1 values (CMD, 2.53 ± 0.37% vs. control, 6.00 ± 0.64% vs. Sham, 6.07 ± 0.97%, p < 0.001) and MPRI (CMD, 1.45 ± 0.13 vs. control, 1.94 ± 0.23, vs. sham, 1.89 ± 0.15, p < 0.001) were both lower in CMD rabbits compared with sham-operated and control rabbits. Further, the stress ΔT1 showed a high correlation with CVF (r = −0.806, p < 0.001) and MVD (r = 0.920, p < 0.001). ConclusionsStress T1 response strongly correlates with pathological MVD and CVF, indicating that stress CMR T1 mapping can accurately detect microvascular dysfunction.

Allicin Improves Hepatic Fibrosis by Regulating Notch 1 Pathway

Aim: To discuss effects and mechanisms of allicin in hepatic fibrosis by vivo study. Materials and methods: Dividing 45 rats into 5 groups. Evaluating pathology and fibrosis by HE and Masson staining, measuring α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression by IHC assay and WB assay; LC 3B protein expression were evaluated by Immunofluorescence. Liver function were measured by Elisa assay. Results: With Allicin supplement, rats’ liver function, pathological and Collagen volume fraction were significantly improved with doses-dependent in liver tissues (P &lt; 0.05, respectively); α-SMA, Collage III, Notch 1, p-AKT and p-mTOR protein expression were significantly suppressed with doses-dependent (P &lt; 0.05, respectively); LC 3B protein expression was significantly increased with doses-dependent (P &lt; 0.05, respectively). Conclusion: Allicin improved hepatic fibrosis by authophagy up regulation via regulation Notrch1/AKT/mTOR pathway by vivo study.

ХАРАКТЕРИСТИКА СОСТОЯНИЯ МИОКАРДА И ПРОФИБРОТИЧЕСКИХ ФАКТОРОВ ПРИ РАЗВИТИИ ГИПЕРТОНИЧЕСКОГО СЕРДЦА

Introduction. Myocardial damage caused by arterial hypertension is manifested by changes in myocardial geometry and mass, as well as increased content of collagen and fibrous tissue in the myocardium. Excessive accumulation of collagen in myocardium is the result of imbalance between proteolytic enzymes such as matrix metalloproteinases 1 (MMP-1) and tissue inhibitors of matrix metalloproteinase 1 (TIMMP-1), high content of transforming growth factor β1 (TFG-β1), which was found in fibroblasts and macrophages. Aim. The aim of the study was to investigate the role of MMP-1 activation, its tissue inhibitor TIMMP-1 and TGF-β1 in blood in the development of myocardial fibrosis in locomotive train workers with arterial hypertension. Material and methods. 82 patients with arterial hypertension and 20 virtually healthy control subjects were examined. The patients of the analyzed groups underwent evaluation of the data of daily blood pressure monitoring, echocardiographic examination, based on which the types of left ventricular remodeling, the content of matrix metalloproteinase 1 and its tissue inhibitor activity, the level of transforming growth factor β1 in blood serum were identified. Calculation of the volume fraction of interstitial collagen was performed. Results and discussion. The study established statistically significant signs of structural changes in the left ventricular myocardium, which primarily indicated its marked left ventricular hypertrophy against the background of arterial hypertension due to chronic pressure overload. Statistically significant increase of all levels of serum markers of collagen metabolism was revealed in patients with arterial hypertension in comparison with the control group. Patients with arterial hypertension have a restructuring of the intercellular matrix components and imbalance in the MMP-1/TIMMP-1 system characterized by a shift of the collagen balance towards fibrosis (increase of THF-β1, TIMMP-1 level, decrease of MMP-1/TIMMP-1 52 ВЕСТНИК СОВРЕМЕННОЙ КЛИНИЧЕСКОЙ МЕДИЦИНЫ 2021 Том 14, вып. 6ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ ratio and increase of interstitial collagen volume fraction). Significant increase of interstitial collagen volume fraction index in the group of patients with arterial hypertension comparing to the control group also indirectly indicates high intensity of interstitial collagen genesis in myocardium of these patients. Conclusion. In arterial hypertension, serum levels of THF-β1, MMP-1, and TIMMP-1 increase, which indirectly indicates an increase in myocardial collagen content.

Effect of PD-1 Inhibitor on Cardiac Inflammatory Microenvironment and Radiation Induced Heart Injury

Effect of PD-1 Inhibitor on Cardiac Inflammatory Microenvironment and Radiation Induced Heart Injury