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- Kovacs, T, et al.
(författare)
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A conserved MTMR lipid phosphatase increasingly suppresses autophagy in brain neurons during aging
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 21817-
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Tidskriftsartikel (refereegranskat)abstract
- Ageing is driven by the progressive, lifelong accumulation of cellular damage. Autophagy (cellular self-eating) functions as a major cell clearance mechanism to degrade such damages, and its capacity declines with age. Despite its physiological and medical significance, it remains largely unknown why autophagy becomes incapable of effectively eliminating harmful cellular materials in many cells at advanced ages. Here we show that age-associated defects in autophagic degradation occur at both the early and late stages of the process. Furthermore, in the fruit fly Drosophila melanogaster, the myotubularin-related (MTMR) lipid phosphatase egg-derived tyrosine phosphatase (EDTP) known as an autophagy repressor gradually accumulates in brain neurons during the adult lifespan. The age-related increase in EDTP activity is associated with a growing DNA N6-adenine methylation at EDTP locus. MTMR14, the human counterpart of EDTP, also tends to accumulate with age in brain neurons. Thus, EDTP, and presumably MTMR14, promotes brain ageing by increasingly suppressing autophagy throughout adulthood. We propose that EDTP and MTMR14 phosphatases operate as endogenous pro-ageing factors setting the rate at which neurons age largely independently of environmental factors, and that autophagy is influenced by DNA N6-methyladenine levels in insects.
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- Arvidsson, Per, et al.
(författare)
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Systolic-diastolic coupling
- 2022
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Ingår i: Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease. - 9780323913911 ; , s. 227-240
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The normally functioning heart delivers a steady supply of oxygen and nutrients to the body over a broad range of physiological states and loading conditions. Efficient cardiac performance at rest and during exercise is therefore a primary evolutionary directive for survival. The four-chambered heart is primarily a volume pump. It couples systolic and diastolic properties because of simultaneous reciprocal atrial filling and ventricular emptying, resulting in near-constant volume, four-chambered heart pumping with very slight variation (5%–7%) of the pericardial sac contents during one cardiac cycle. This is achieved by oscillatory motion of atrioventricular valve plane, while the epicardial apex and back of the atria remain spatially fixed. Ventricular filling is initiated through the spring-like recoil of the relaxing left ventricular chamber wall (myocardium) and associated tissues, converting part of stored end-systolic elastic strain into wall motion and diastolic suction of atrial blood. In this chapter, functional predictions regarding systolic–diastolic and atrioventricular interactions are presented from a kinematic framework and validated using human imaging and invasive measurements.
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- Arvidsson, Per, et al.
(författare)
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Vortex ring behavior provides the epigenetic blueprint for the human heart.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The laws of fluid dynamics govern vortex ring formation and precede cardiac development by billions of years, suggesting that diastolic vortex ring formation is instrumental in defining the shape of the heart. Using novel and validated magnetic resonance imaging measurements, we show that the healthy left ventricle moves in tandem with the expanding vortex ring, indicating that cardiac form and function is epigenetically optimized to accommodate vortex ring formation for volume pumping. Healthy hearts demonstrate a strong coupling between vortex and cardiac volumes (R(2) = 0.83), but this optimized phenotype is lost in heart failure, suggesting restoration of normal vortex ring dynamics as a new, and possibly important consideration for individualized heart failure treatment. Vortex ring volume was unrelated to early rapid filling (E-wave) velocity in patients and controls. Characteristics of vortex-wall interaction provide unique physiologic and mechanistic information about cardiac diastolic function that may be applied to guide the design and implantation of prosthetic valves, and have potential clinical utility as therapeutic targets for tailored medicine or measures of cardiac health.
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- Maksuti, Elira, 1986-, et al.
(författare)
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Hydraulic forces contribute to left ventricular diastolic filling
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75-100% of diastole. The hydraulic force was the same order of magnitude as the peak driving force of LV (1-3N vs 5-10N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the resulting hydraulic forces, should be considered when characterizing diastolic function and dysfunction.
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- Maksuti, Elira, et al.
(författare)
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Hydraulic forces contribute to left ventricular diastolic filling
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 43505-43505
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75-100% of diastole. The hydraulic force was estimated to be 10-60% of the peak driving force of LV filling (1-3 N vs 5-10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction.
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