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  • Ovid Technologies (Wolters Kluwer Health)  (3)
  • 1
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 134, No. 10 ( 2024-05-10), p. 1240-1255
    Abstract: Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown. METHODS: In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts. RESULTS: Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of Rgs5 was reduced in cardiac pericytes from aged mice. In vivo and in vitro studies showed that the deletion of RGS5 impaired cardiac function, induced fibrosis, and morphological changes in pericytes characterized by a profibrotic gene expression signature and the expression of different ECM (extracellular matrix) components and growth factors, for example, TGFB2 and PDGFB . Indeed, culturing fibroblasts with the supernatant of RGS5-deficient pericytes induced their activation as evidenced by the increased expression of αSMA (alpha smooth muscle actin) in a TGFβ (transforming growth factor beta)2-dependent mechanism. CONCLUSIONS: Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467838-X
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Current Opinion in Lipidology Vol. 33, No. 6 ( 2022-12), p. 353-363
    In: Current Opinion in Lipidology, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 6 ( 2022-12), p. 353-363
    Abstract: Aging is an important risk factor for cardiovascular disease and is associated with increased vessel wall stiffness. Pathophysiological stiffening, notably in arteries, disturbs the integrity of the vascular endothelium and promotes permeability and transmigration of immune cells, thereby driving the development of atherosclerosis and related vascular diseases. Effective therapeutic strategies for arterial stiffening are still lacking. Recent findings Here, we overview the literature on age-related arterial stiffening, from patient-derived data to preclinical in-vivo and in-vitro findings. First, we overview the common techniques that are used to measure stiffness and discuss the observed stiffness values in atherosclerosis and aging. Next, the endothelial response to stiffening and possibilities to attenuate this response are discussed. Summary Future research that will define the endothelial contribution to stiffness-related cardiovascular disease may provide new targets for intervention to restore endothelial function in atherosclerosis and complement the use of currently applied lipid-lowering, antihypertensive, and anti-inflammatory drugs.
    Type of Medium: Online Resource
    ISSN: 0957-9672 , 1473-6535
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2026990-0
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  • 3
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 3 ( 2021-02-02)
    Abstract: Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with a deterioration of clinical status. Ablation of symptomatic AF is an established therapy, but in HCM, the characteristics of recurrent atrial arrhythmias and the long‐term outcome are uncertain. Methods and Results Sixty‐five patients with HCM (aged 64.5±9.9 years, 42 [64.6%] men) underwent AF ablation. The ablation strategy included pulmonary vein isolation in all patients and ablation of complex fractionated atrial electrograms or subsequent atrial tachycardias (AT) if appropriate. Paroxysmal, persistent AF, and a primary AT was present in 13 (20.0%), 51 (78.5%), and 1 (1.5%) patients, respectively. Twenty‐five (38.4%) patients developed AT with a total number of 54 ATs. Stable AT was observed in 15 (23.1%) and unstable AT in 10 (15.3%) patients. The mechanism was characterized as a macroreentry in 37 (68.5%), as a localized reentry in 12 (22.2%), a focal mechanism in 1 (1.9%), and not classified in 4 (7.4%) ATs. After 1.9±1.2 ablation procedures and a follow‐up of 48.1±32.5 months, freedom of AF/AT recurrences was demonstrated in 60.0% of patients. No recurrences occurred in 84.6% and 52.9% of patients with paroxysmal and persistent AF, respectively ( P 〈 0.01). Antiarrhythmic drug therapy was maintained in 24 (36.9%) patients. Conclusions AF ablation in patients with HCM is effective for long‐term rhythm control, and especially patients with paroxysmal AF undergoing pulmonary vein isolation have a good clinical outcome. ATs after AF ablation are frequently observed in HCM. Freedom of atrial arrhythmia is achieved by persistent AF ablation in a reasonable number of patients even though the use of antiarrhythmic drug therapy remains high.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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