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Browsing Material embargado by browse.metadata.categoria "Medicina y salud"

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    Contribution of medullary pre-sympathetic neurons on cardiovascular dysfunction during transition to menopause
    (2025) Schwarz Flores, Karla Gabriele; Río Troncoso, Rodrigo Andre del; Inestrosa Cantín, Nibaldo; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    Cardiovascular disease is a highly prevalent condition in middle-aged women and are among the leading cause of poor patient’s quality of life and is recognized as the woman’s greatest health threat. Importantly, recent evidence suggests the existence of an intimate crosstalk between the heart and the brain, resulting from a complex network of neurohumoral circuits. From a pathophysiological perspective, the higher prevalence of heart disease in elderly women, may be explained in part by sex-related differences in cardiovascular disease’s risk factors. The autonomic nervous system is a major physiological actor affecting heart-brain axis in health and disease. Importantly, accumulating evidence support the negative impact of decreased estrogen due to menopause transition as a risk factor for adverse cardiovascular events, possibly contributing to autonomic imbalance in middle-aged women, however this hypothesis has not been comprehensive tested before. Central autonomic nuclei, such as the rostral ventrolateral medulla (RVLM) encompasses a pivotal circuit of control of sympathetic flow and blood pressure. Overactivity of sympathetic tone is a hallmark of cardiovascular disorders, including hypertension, stroke and HF. In fact, it was suggested that estrogens exert direct effects on RVLM through estrogen receptors (ERα and ERβ), thereby leading to sympathoinhibitory effects, which may be crucial for cardiovascular protection. While a strong causal-association between sympathetic overactivity and development of cardiovascular diseases has been previously established, further interdisciplinary studies are needed to better understand the underlying cellular/molecular and physiological mechanisms, particularly in the perimenopausal and postmenopausal women. If a reduced estrogen signaling through neuronal ERs contributes to aberrant pre-sympathetic neural activity during menopause leads to autonomic imbalance, cardiovascular disorders and exercise capacity remains totally unknown. My underlying hypothesis is that normalizing autonomic nervous function during perimenopause will have a positive impact on cardiac function in experimentally healthy menopause. I proposed an integrative approach by combining freely moving animal recordings, chemogenetic and hormone treatment to assess cardiovascular/autonomic function in a preclinical model of menopause transition using 4-vinylcyclohexane- mediated accelerated ovarian failure. Furthermore, cellular and molecular mechanisms associated with ERs signaling were elucidated using in vitro model of menopause. In this proposal, I determined, for the first time that, i) estrogen decrease during perimenopause triggers brainstem pre-sympathetic neurons (RVLM C1) overactivity WT mice, leading to cardiac autonomic imbalance, arrhythmogenesis and cardiac diastolic and systolic dysfunction; ii) RVLM C1 neurons contribute to cardiac sympathetic overactivity, cardiac arrythmias and cardiac impairment in postmenopausal mice; iii) long-term 17β-estradiol treatment during perimenopause decrease RVLM C1 activity, improving cardiac function in postmenopausal stage. Together, the results suggest that RVLM C1 neurons play a major role in cardiovascular remodeling during female reproductive senescence.
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    Exploring metabolic dysfunction-associated steatotic liver disease in lean individuals from Chile: Analysis of metabolic and genetic parameters
    Ayala Valverde, María; Arrese, Marco; Pontificia Universidad Católica de Chile. Facultad de Medicina
    Introduction: Steatotic liver disease associated with metabolic dysfunction (MASLD) is the most common liver disease in the world. Obesity is the most relevant risk factor, but MASLD can also be observed in people with normal weight. Aim: This study aimed to analyze the features of MASLD in Chilean patients with normal body mass index (BMI) and particularly the frequency of the rs738409 risk polymorphism in Chilean individuals with hepatic steatosis. Methods: A cross-sectional study was conducted involving 181 randomly selected participants diagnosed with MASLD from the prospective Maule Cohort (MAUCO). Participants were categorized into lean, overweight, and obese groups based on their BMI. The presence of the rs738409 polymorphism was examined using Sanger sequencing. Statistical analyses of clinical data and genotypes encompassed Fisher's exact test, Chi-square test, Kruskal-Wallis test, and prevalence analysis. Results: 31.49% (57) were classified as thin, 36.3% (61) as overweight and 39.8% (67) as obese. Apart from higher ALT levels (p=0.004) and body fat percentage in obese subjects, no significant differences were found between the groups in terms of clinical characteristics or comorbidities. The allelic frequency of rs738409 was 77.1%, 83.6% and 82.5% in lean, overweight, and obese subjects, respectively, with no significant differences evident. Conclusions: In this sample of Chilean subjects with MASLD there were no significant differences linked to BMI with respect to the clinical characteristics of MASLD or the allele frequency of rs738409. Nevertheless, lean subjects with MASLD share cardiometabolic characteristics when compared to overweight and obese individuals.