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• W4229080014 abstract "Myocardial fibrosis is a remodeling process of the extracellular matrix (ECM) following cardiac stress. “Replacement fibrosis” is a term used to describe wound healing in the acute phase of an injury, such as myocardial infarction. In striking contrast, ECM remodeling following chronic pressure overload insidiously develops over time as “reactive fibrosis” leading to diffuse interstitial and perivascular collagen deposition that continuously perturbs the function of the left (L) or the right ventricle (RV). Examples for pressure-overload conditions resulting in reactive fibrosis in the LV are systemic hypertension or aortic stenosis, whereas pulmonary arterial hypertension (PAH) or congenital heart disease with right sided obstructive lesions such as pulmonary stenosis result in RV reactive fibrosis. In-depth phenotyping of cardiac fibrosis has made it increasingly clear that both forms, replacement and reactive fibrosis co-exist in various etiologies of heart failure. While the role of fibrosis in the pathogenesis of RV heart failure needs further assessment, reactive fibrosis in the LV is a pathological hallmark of adverse cardiac remodeling that is correlated with or potentially might even drive both development and progression of heart failure (HF). Further, LV reactive fibrosis predicts adverse outcome in various myocardial diseases and contributes to arrhythmias. The ability to effectively block pathological ECM remodeling of the LV is therefore an important medical need. At a cellular level, the cardiac fibroblast takes center stage in reactive fibrotic remodeling of the heart. Activation and proliferation of endogenous fibroblast populations are the major source of synthesis, secretion, and deposition of collagens in response to a variety of stimuli. Enzymes residing in the ECM are responsible for collagen maturation and cross-linking. Highly cross-linked type I collagen stiffens the ventricles and predominates over more elastic type III collagen in pressure-overloaded conditions. Research has attempted to identify pro-fibrotic drivers causing fibrotic remodeling. Single key factors such as Transforming Growth Factor β (TGFβ) have been described and subsequently targeted to test their usefulness in inhibiting fibrosis in cultured fibroblasts of the ventricles, and in animal models of cardiac fibrosis. More recently, modulation of phenotypic behaviors like inhibition of proliferating fibroblasts has emerged as a strategy to reduce pathogenic cardiac fibroblast numbers in the heart. Some studies targeting LV reactive fibrosis as outlined above have successfully led to improvements of cardiac structure and function in relevant animal models. For the RV, fibrosis research is needed to better understand the evolution and roles of fibrosis in RV failure. RV fibrosis is seen as an integral part of RV remodeling and presents at varying degrees in patients with PAH and animal models replicating the disease of RV afterload. The extent to which ECM remodeling impacts RV function and thus patient survival is less clear. In this review, we describe differences as well as common characteristics and key players in ECM remodeling of the LV vs. the RV in response to pressure overload. We review pre-clinical studies assessing the effect of anti-fibrotic drug candidates on LV and RV function and their premise for clinical testing. Finally, we discuss the mode of action, safety and efficacy of anti-fibrotic drugs currently tested for the treatment of left HF in clinical trials, which might guide development of new approaches to target right heart failure. We touch upon important considerations and knowledge gaps to be addressed for future clinical testing of anti-fibrotic cardiac therapies." @default.
• W4229080014 created "2022-05-08" @default.
• W4229080014 creator A5001067636 @default.
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• W4229080014 date "2022-05-06" @default.
• W4229080014 modified "2023-10-18" @default.
• W4229080014 title "Cardiac Fibrosis in the Pressure Overloaded Left and Right Ventricle as a Therapeutic Target" @default.
• W4229080014 cites W110354215 @default.
• W4229080014 cites W121290665 @default.
• W4229080014 cites W124750557 @default.
• W4229080014 cites W1669479280 @default.
• W4229080014 cites W1676600749 @default.
• W4229080014 cites W1801975325 @default.
• W4229080014 cites W1872516364 @default.
• W4229080014 cites W1897878823 @default.
• W4229080014 cites W1965943806 @default.
• W4229080014 cites W1967340614 @default.
• W4229080014 cites W1968903007 @default.
• W4229080014 cites W1970248508 @default.
• W4229080014 cites W1971362991 @default.
• W4229080014 cites W1974848384 @default.
• W4229080014 cites W1976052678 @default.
• W4229080014 cites W1983996730 @default.
• W4229080014 cites W1986660466 @default.
• W4229080014 cites W1986967085 @default.
• W4229080014 cites W1988823494 @default.
• W4229080014 cites W1989375528 @default.
• W4229080014 cites W1990163699 @default.
• W4229080014 cites W1990428828 @default.
• W4229080014 cites W1993869526 @default.
• W4229080014 cites W1998562191 @default.
• W4229080014 cites W2000088166 @default.
• W4229080014 cites W2002636102 @default.
• W4229080014 cites W2004656949 @default.
• W4229080014 cites W2004866985 @default.
• W4229080014 cites W2005457797 @default.
• W4229080014 cites W2005673278 @default.
• W4229080014 cites W2012373573 @default.
• W4229080014 cites W2015001608 @default.
• W4229080014 cites W2023314610 @default.
• W4229080014 cites W2024690705 @default.
• W4229080014 cites W2024874419 @default.
• W4229080014 cites W2025717721 @default.
• W4229080014 cites W2026329716 @default.
• W4229080014 cites W2027082110 @default.
• W4229080014 cites W2028933935 @default.
• W4229080014 cites W2029023549 @default.
• W4229080014 cites W2030317550 @default.
• W4229080014 cites W2030398090 @default.
• W4229080014 cites W2031137884 @default.
• W4229080014 cites W2031203524 @default.
• W4229080014 cites W2032381326 @default.
• W4229080014 cites W2032990474 @default.
• W4229080014 cites W2033058019 @default.
• W4229080014 cites W2034137026 @default.
• W4229080014 cites W2034315625 @default.
• W4229080014 cites W2035653659 @default.
• W4229080014 cites W2037381436 @default.
• W4229080014 cites W2047970481 @default.
• W4229080014 cites W2049299937 @default.
• W4229080014 cites W2049463386 @default.
• W4229080014 cites W2049763853 @default.
• W4229080014 cites W2050862994 @default.
• W4229080014 cites W2052017836 @default.
• W4229080014 cites W2053083471 @default.
• W4229080014 cites W2054758759 @default.
• W4229080014 cites W2055725306 @default.
• W4229080014 cites W2057108655 @default.
• W4229080014 cites W2057292199 @default.
• W4229080014 cites W2058657865 @default.
• W4229080014 cites W2059762308 @default.
• W4229080014 cites W2064677108 @default.
• W4229080014 cites W2065972506 @default.
• W4229080014 cites W2067152340 @default.
• W4229080014 cites W2068824179 @default.
• W4229080014 cites W2069060200 @default.
• W4229080014 cites W2071251073 @default.
• W4229080014 cites W2074461681 @default.
• W4229080014 cites W2075199540 @default.
• W4229080014 cites W2079740085 @default.
• W4229080014 cites W2080670526 @default.
• W4229080014 cites W2081639542 @default.
• W4229080014 cites W2081878872 @default.
• W4229080014 cites W2082486468 @default.
• W4229080014 cites W2084107184 @default.
• W4229080014 cites W2085730106 @default.
• W4229080014 cites W2085786241 @default.
• W4229080014 cites W2086053451 @default.
• W4229080014 cites W2086690219 @default.
• W4229080014 cites W2087808538 @default.
• W4229080014 cites W2088058903 @default.
• W4229080014 cites W2088776044 @default.
• W4229080014 cites W2089392247 @default.
• W4229080014 cites W2089759938 @default.
• W4229080014 cites W2091872000 @default.
• W4229080014 cites W2098994127 @default.
• W4229080014 cites W2102199009 @default.

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