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Collagen dysfunction

Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
C-F Hsieh, P Alberton, E Loffredo-Verde, E Volkmer, M Pietschmann, P E Müller, M Schieker, D Docheva
Tendon's natural healing potential is extremely low and inefficient, with significant dysfunction and disability due to hypocellularity and hypovascularity of tendon tissues. The application of stem cells can aid in significantly enhanced repair of tendon rupture; therefore, the main aim of this study is to assess the potential of using periodontal ligament cells (PDL), usually obtained from patients undergoing orthodontic treatment, as a novel cell source for cell-based therapy for tendon injuries in a clinically relevant rat full-size Achilles tendon defect...
October 20, 2016: European Cells & Materials
Xin Gu, Bingjie Gu, Xianhui Lv, Zhenzhen Yu, Rong Wang, Xiaoli Zhou, Wanxin Qiao, Zhiyuan Mao, Guoping Zuo, Qing Li, Dengshun Miao, Jianliang Jin
Impaired apoptosis of fibroblast-like synoviocytes (FLSs) causes synovial hyperplasia, facilitating destruction of cartilage and bone in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α, a dominant inflammatory mediator in RA pathogenesis, promotes progression of RA symptoms. Prevalence of 1, 25-dihydroxy-vitamin D3 (hereafter termed VD) deficiency is 30-63% in patients with RA. Whether VD leads to apoptosis or enhances TNF-α-mediated apoptosis in FLSs to ameliorate RA is unclear. To determine this, 10-week-old CYP27B1-deficient (CYP27B1(-/-)) mice with collagen-induced arthritis (CIA) were intraperitoneally treated with 1 μg/kg VD every other day for 9 weeks...
October 20, 2016: Cell Death & Disease
Tadashi Kawai, Yuji Tanuma, Keiko Matsui, Osamu Suzuki, Tetsu Takahashi, Shinji Kamakura
It was demonstrated that octacalcium phosphate collagen composite achieved notable bone regeneration in bone defects in preclinical studies. On the basis of the research results, an investigator-initiated exploratory clinical trial was conducted after approval from a local Institutional Review Board. This clinical study was performed as a single-arm non-randomized intervention study. Octacalcium phosphate collagen composite was implanted into a total of 10 cases of alveolar bone defects after tooth extractions and cystectomy...
January 2016: Journal of Tissue Engineering
V V Muthusamy
Cardiovascular disease burden is increasing all over the world. The diagnosis of hypertension is considered when a person has persistently elevated BP (Systolic BP more than 140 mmHg and/or Diastolic BP more than 90 mmHg). Dyslipidemia denotes abnormal levels of lipids in the blood (Total Cholesterol >200 mg%, Low density lipoprotein (LDL) >100 mg%, Triglycerides (TGL) >150 mg% and High density lipoprotein (HDL) <40 mg in men and < 50 mg in women. Hypertension and Dyslipidemia constitute the important components of metabolic syndrome as per the definition of NCEP Guidelines-Adult Treatment Panel III (ATP III)...
September 2016: Journal of Hypertension
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Xiaodong Li, Mona Hong, Dingliang Zhu, Pingjin Gao
OBJECTIVE: The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. DESIGN AND METHOD: Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II infusion (200 ng/kg/min) in male Sprague-Dawley rats...
September 2016: Journal of Hypertension
Francisco J Rios, Katie Y Hood, A Karvey, Karla B Neves, Panagiota Anyfanti, Ryszard Nosalski, Livia L Camargo Ll, Augusto C Montezano, Rhian M Touyz
OBJECTIVE: TRPM7 is cation channel with intrinsic kinase activity important for cellular Mg homeostasis. We recently showed that TRPM7-kinase plays a role in aldosterone-mediated vascular effects and inflammation. Here we explored the putative role of TRPM7-kinase in cardiac fibrosis and vascular function in aldosterone-induced hypertension in mice. DESIGN AND METHOD: Wild-type (WT) or heterozygote TRPM7-kinase domain (TRPM7+/-) mice were treated with infused aldosterone (600 μg/Kg/day) and NaCl 1% in drinking water (aldo/salt) for 4 weeks...
September 2016: Journal of Hypertension
Che Wei Liao, Chi Sheng Hung, Chia Hung Chou, Yen Tin Lin, Xue Ming Wu, Yi Yao Chang, Ying Hsien Chen, Vin Cent Wu, Yi Lwun Ho, Kwan Dun Wu, Yen Hung Lin
OBJECTIVE: Aldosterone induces myocardial fibrosis. The tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis and diastolic dysfunction, but the effect of aldosterone on TIMP-1 expression remains unclear. We tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. DESIGN AND METHOD: In the human study, we prospectively enrolled 54 patients with primary aldosteronism. Plasma TIMP-1 and echocardiographic parameters were measured...
September 2016: Journal of Hypertension
Enrico Agabiti Rosei
Current Hypertension Guidelines emphasize the importance of assessing the presence of preclinical organ damage. In fact, an extensive evaluation of organ damage may increase the number of patients classified at high CV risk and therefore strongly influence the clinical management of patients. Hypertensive heart disease remains to date the form of organ damage for which there is the greatest amount of evidence of a strong independent prognostic significance. In the presence of a chronic pressure overload, a parallel addition of sarcomers takes place with an increase in myocyte width, which in turn increases left ventricular wall thickness; myocyte hypertrophy is also associated with apoptosis, collagen deposition and ventricular fibrosis with an impairment of coronary hemodynamics as well, thus profoundly influencing functional properties of the left (and right) ventricle...
September 2016: Journal of Hypertension
Joyce Bischoff, Guillem Casanovas, Jill Wylie-Sears, Dae-Hee Kim, Philipp Bartko, J Guerrero, Jacob Dal-Bianco, Jonathan Beaudoin, Michael Garcia, Suzanne Sullivan, Margo Seybolt, Brittan Morris, Joshua Keegan, Whitney Irvin, Elena Aikawa, Robert Levine
RATIONALE: Ischemic mitral regurgitation (IMR), a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial, but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to IMR. OBJECTIVE: Endothelial, interstitial and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post-MI, was analyzed in vitro...
October 6, 2016: Circulation Research
Blazej Michalski, Przemyslaw Trzcinski, Karolina Kupczynska, Dawid Miskowiec, Lukasz Peczek, Barbara Nawrot, Piotr Lipiec, Jaroslaw D Kasprzak
BACKGROUND: The aim of the study was to assess the correlation of the selected biomarkers and collagen turn-over indices with advanced echocardiographic parameters among patients with preserved and reduced ejection fraction (EF). METHODS: We included 62 patients with the symptomatic heart failure. The patients were divided in to two groups according to the evaluated ejection fraction (EF - Simpson method): heart failure with reduced ejection fraction (HFrEF) group - 30 patients with low EF - 35-50% (16 male, mean age 54...
October 17, 2016: Cardiology Journal
Yuan Ma, Jia-Xiang Zhang, Ya-Nan Liu, Ai Ge, Hao Gu, Wang-Jian Zha, Xiao-Ning Zeng, Mao Huang
In the pathophysiology of asthma, structural cell dysfunction and concomitant microenvironment changes in airways are crucial to pathological progression, which involves oxidative stress. Caffeic acid phenethyl ester (CAPE) is an active anti-oxidative component obtained from propolis, and has been shown to have beneficial effects on several respiratory disorders, such as chronic obstructive pulmonary disease and lung cancer. However, the impact of CAPE on asthma is not well understood. Therefore, this study investigated the advantages of using CAPE to treat asthma and demonstrated the roles of CAPE in the regulation of airway microenvironments...
October 13, 2016: Free Radical Biology & Medicine
Rugmani Padmanabhan Iyer, Lisandra E de Castro Brás, Nicolle L Patterson, Manishabrata Bhowmick, Elizabeth R Flynn, Majdouline Asher, Presley L Cannon, Kristine Y Deleon-Pennell, Gregg B Fields, Merry L Lindsey
Matrix metalloproteinase-9 (MMP-9) is robustly elevated in the first week post-myocardial infarction (MI). Targeted deletion of the MMP-9 gene attenuates cardiac remodeling post-MI by reducing macrophage infiltration and collagen accumulation through increased apoptosis and reduced inflammation. In this study, we used a translational experimental design to determine whether selective MMP-9 inhibition early post-MI would be an effective therapeutic strategy in mice. We enrolled male C57BL/6J mice (3-6months old, n=116) for this study...
October 13, 2016: Journal of Molecular and Cellular Cardiology
Cristiane C Denardin, Leo A M Martins, Mariana M Parisi, Moema Queiroz Vieira, Silvia R Terra, Florencia M Barbé-Tuana, Radovan Borojevic, Márcia Vizzotto, Tatiana Emanuelli, Fátima Costa Rodrigues Guma
Activated hepatic stellate cells (HSC) are the major source of collagen I in liver fibrosis. Eugenia uniflora L. is a tree species that is widely distributed in South America. E. uniflora L. fruit-popularly known as pitanga-has been shown to exert beneficial properties. Autophagy contributes to the maintenance of cellular homeostasis and survival under stress situation, but it has also been suggested to be an alternative cell death pathway. Mitochondria play a pivotal role on signaling cell death. Mitophagy of damaged mitochondria is an important cell defense mechanism against organelle-mediated cell death signaling...
October 15, 2016: Cell Biology and Toxicology
Saba Farnaghi, Indira Prasadam, Guangping Cai, Thor Friis, Zhibin Du, Ross Crawford, Xinzhan Mao, Yin Xiao
The contribution of metabolic factors on the severity of osteoarthritis (OA) is not fully appreciated. This study aimed to define the effects of hypercholesterolemia on the progression of OA. Apolipoprotein E-deficient (ApoE(-/-)) mice and diet-induced hypercholesterolemic (DIHC) rats were used to explore the effects of hypercholesterolemia on the progression of OA. Both models exhibited OA-like changes, characterized primarily by a loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and cartilage degradation...
October 13, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hui Zhao, Wei Wang, Jie Zhang, Tuo Liang, Guang-Pu Fan, Zhi-Wei Wang, Pei-De Zhang, Xu Wang, Jing Zhang
BACKGROUND: Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to a close relationship with cardiac fibrosis. Overexpression of OPN in cardiomyocytes induces dilated cardiomyopathy (DCM). This research is to study whether inhibition of OPN could reduce myocardial remodelling in DCM, and if this process is focal adhesion kinase (FAK) dependent, which is recently found an important signal molecule in fibrosis. METHOD: Eight-week-old cTnTR(141W) transgenic mouse of DCM were injected with OPN-shRNA in left ventricular free wall, which could inhibit the OPN expression...
2016: American Journal of Translational Research
Hirak Biswas, Gregory D Longmore
Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level...
2016: PloS One
Mark S Cook, Laura Bou-Malham, Mary C Esparza, Marianna Alperin
INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle rehabilitation is a widely utilized, but often challenging therapy for pelvic floor disorders, which are prevalent in older women. Regimens involving the use of appendicular muscles, such as the obturator internus (OI), have been developed for strengthening of the levator ani muscle (LAM). However, changes that lead to potential dysfunction of these alternative targets in older women are not well known. We hypothesized that aging negatively impacts OI architecture, the main determinant of muscle function, and intramuscular extracellular matrix (ECM), paralleling age-related alterations in LAM...
October 4, 2016: International Urogynecology Journal
Ram P Naikawadi, Supparerk Disayabutr, Benat Mallavia, Matthew L Donne, Gary Green, Janet L La, Jason R Rock, Mark R Looney, Paul J Wolters
Telomeres are short in type II alveolar epithelial cells (AECs) of patients with idiopathic pulmonary fibrosis (IPF). Whether dysfunctional telomeres contribute directly to development of lung fibrosis remains unknown. The objective of this study was to investigate whether telomere dysfunction in type II AECs, mediated by deletion of the telomere shelterin protein TRF1, leads to pulmonary fibrosis in mice (SPC-Cre TRF1(fl/fl) mice). Deletion of TRF1 in type II AECs for 2 weeks increased γH2AX DNA damage foci, but not histopathologic changes in the lung...
September 8, 2016: JCI Insight
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