Action and therapeutic targets of myosin light chain kinase, an important cardiovascular signaling mechanism

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107276 - 107276

Published: June 27, 2024

The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. pathogenesis cardiovascular disease complex and not fully understood, the physiological function heart inextricably linked to well-regulated muscle movement. Myosin light chain kinase (MLCK) essential for myocardial contraction diastole, electrophysiological homeostasis, vasoconstriction vascular nerves blood pressure regulation. In this sense, MLCK appears be an attractive therapeutic target diseases. participates in cell movement migration through diverse pathways, including regulation calcium activation myosin phosphorylation, stimulation smooth or relaxation. Recently, phosphorylation chains has been shown closely associated with exercise signaling, mediates systolic diastolic functions interaction thick filaments actin thin filaments. It works by upholding integrity cytoskeleton, modifying conformation head, modulating innervation. governs adrenergic sympathetic nervous systems, extracellular transport, endothelial permeability, nitric oxide angiotensin II. Additionally, plays crucial role process aging. Multiple natural products/phytochemicals chemical compounds, such as quercetin, cyclosporin, ML-7 hydrochloride, have regulate cardiomyocyte MLCK. MLCK-modifying capacity these compounds should considered designing novel agents. This review summarizes mechanism action system potential reported processes.

Language: Английский

---

Adolescent Cardiorespiratory Fitness and Future Work Ability

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(3), P. e243861 - e243861

Published: March 27, 2024

Importance Although research indicates that low fitness in youth is associated with a higher risk of chronic disability men, the association adolescence work ability working men and women remains unknown. Objective To examine associations adolescent health-related physical future ability. Design, Setting, Participants This 45-year observational cohort study, conducted Finland, examined direct indirect longitudinal objectively measured (in 1976) self-reported sickness absence early middle age 2001) Work Ability Index late 2021). A countrywide stratified random baseline sample included measurements for cardiorespiratory (CRF) (running 1.5 km girls 2 boys), musculoskeletal (MF; standing broad jump sit-ups both sexes, pull-ups boys, flexed-arm hang girls), height weight, from which body mass index (BMI) was calculated. Structural equation modeling–based path analysis, adjusted sex at educational level, work-related strain, leisure-time activity age, conducted. Data analysis performed January to July 2023. Main Outcomes Measures Self-reported structured questions validated age. Results The final analyses (1207 individuals; 579 [48%] male individuals) consisted participants measurement 12 19 years, assessment 37 44 years and/or 57 64 years. Higher CRF (839 participants; β = 0.12; 95% CI, 0.01 0.22; P .03) lower (834 −0.07; −0.12 −0.02; .004) and, indirectly, mediated by end (603 0.04; 0.001 0.08; .04). results remained consistent sexes after adjustment confounders. Neither MF nor BMI (MF, 1192 −0.17 0.03; BMI, 1207 participants, 0.09; −0.004 0.19) or 1185 0.02; −0.03 0.06; 1202 −0.03; −0.09 0.03) ability, 603 −0.06 0.01; 0.07). Conclusions Relevance These findings suggest poor life, highlights informative prognostic value youth. Enhancing first decades life might contribute better capacity productivity labor force, would have implications health, quality society, economy.

Language: Английский

---

Editorial: The interaction of physical activity, genetic and environmental factors on cardiovascular health

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: April 29, 2025

Language: Английский

---

Adolescent cardiorespiratory fitness and risk of cancer in late adulthood: A nationwide sibling-controlled cohort study in Sweden

PLoS Medicine, Journal Year: 2025, Volume and Issue: 22(5), P. e1004597 - e1004597

Published: May 8, 2025

Background Cardiorespiratory fitness has been linked to both lower and higher risks of cancer, but the evidence comes from observational analysis which may be influenced by unobserved confounders bias processes. We aimed examine associations between adolescent cardiorespiratory risk cancer in late adulthood while addressing unknown influence familial diagnostic Methods findings conducted a sibling-controlled cohort study with registry linkage based on all Swedish men who participated mandatory military conscription examinations 1972 1995 completed standardized testing. The outcomes were overall diagnosis mortality, 14 site-specific cancers (diagnosis or death), ascertained using National Patient Register Cause Death until 31 December 2023. A total 1,124,049 men, including 477,453 full siblings, mean age 18.3 years at baseline, followed median (maximum) 55.9 (73.5) years, during 98,410 diagnosed 16,789 died (41,293 6,908 among siblings respectively). In analysis, individuals highest quartile had mortality (adjusted hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.67, 0.76; P < 0.001) compared lowest quartile, corresponding cumulative incidence (1-Survival) difference −0.85 (95% CI [−1.00, −0.71]) percentage points 65 age. Individuals also (HRs ranging 0.81 0.49, differences −0.13 −0.32 points; 0.001 for all) rectum, head neck, bladder, stomach, pancreas, colon, kidney, liver, bile ducts, gallbladder, esophagus, lung cancer. Yet, prostate (HR: 1.10, [1.05, 1.16]; 0.001, difference: 0.48 points, [0.23, 0.73]) skin (e.g., non-melanoma HR: 1.44, [1.38, 1.50]; 1.84 [1.62, 2.05]). 1.08, [1.06, 1.11]; 1.32 [0.94, 1.70]), results driven being most common types When comparing thereby controlling shared confounders, remained 0.78, [0.68, 0.89]; −0.61 [−0.93, −0.28]), excess 1.01, [0.90, 1.13]; = 0867, 0.05 [−0.50, 0.60]), 1.09, [0.99, 1.20]; 0.097, 0.40 [−0.07, 0.87]), 1.00, [0.95, 1.06]; 0.921, 0.04 [−0.80, 0.88]) attenuated null. For other cancers, sibling comparisons varied, more attenuation melanoma, gallbladder lung, esophagus seemed attenuate less. confirmed through an extensive set sensitivity analyses. main limitations this include lack inclusion female participants, data factors such as smoking, alcohol consumption, physical activity, only adjustment are siblings. Conclusions Higher levels associated adulthood, finding that persisted comparisons. However, confounding appeared vary type pronounced diagnoses than mortality. This suggest need robust causal methods triangulate results, rather relying correlations alone, better inform public health efforts.

Language: Английский

---

Family matters: rethinking cardiovascular health promotion through a household lens

European Journal of Cardiovascular Nursing, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Language: Английский

---

Low physical activity level in out-of-hospital cardiac arrest survivors with obesity, mobility problems and cognitive impairment: Results from the TTM2 trial

Resuscitation, Journal Year: 2024, Volume and Issue: 204, P. 110407 - 110407

Published: Oct. 4, 2024

Language: Английский

---

Overweight and obesity among Israeli adolescents and the risk for serious morbidity in early young adulthood: a nationwide retrospective cohort study

The Lancet Diabetes & Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

---

Adolescent Cardiorespiratory Fitness and Risk of Cancer in Late Adulthood: Nationwide Sibling-Controlled Cohort Study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

To investigate whether the higher risks of certain cancers associated with high cardiorespiratory fitness can be explained by increased detection and unobserved confounders.

Language: Английский

---

Cardiorespiratory Fitness in Adolescence and Risk of Type 2 Diabetes in Late Adulthood: A Nationwide Sibling-Controlled Cohort Study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Summary Background The importance of adolescent cardiorespiratory fitness for long-term risk type 2 diabetes (T2D) remains poorly investigated, and whether the association is influenced by unobserved familial confounding unknown. Methods We conducted a sibling-controlled cohort study based on all Swedish men who participated in mandatory military conscription examinations from 1972 to 1995 around age 18, completed standardized testing. outcome was T2D, defined as composite endpoint diagnosis inpatient or specialist outpatient care, dispensation antidiabetic medication, until 31 December 2023. Findings 1 124 049 men, which 477 453 were full siblings, with mean 18.3 years at baseline included. During follow-up, 115 958 (48 089 siblings) experienced first T2D event median 53.4 years. Compared decile fitness, higher levels associated progressively lower T2D. In analysis, hazard ratio (HR) second 0.83 (95% CI, 0.81 0.85), difference cumulative incidence 65 4.3 (3.8 4.8) percentage points, dropping HR 0.38 (0.36 0.39; 17.8 [17.3 18.3] points) tenth decile. When comparing thus controlling behavioral, environmental, genetic confounders that they share, replicated, although attenuation magnitude. 0.89 (0.85 0.94; 2.3 [1.3 3.3] points), it 0.53 (0.50 0.57; 10.9 [9.7 12.1] points). Hypothetically shifting everyone estimated prevent 7.2% (6.4 8.0) cases vs. 4.6% (2.6 6.5) full-sibling analysis. similar those overweight without. Interpretation Higher are late adulthood, clinically relevant associations starting already very low similarly compared replicates, but becomes weaker, after adjusting shared between siblings. This suggests robust marker risk, conventional observational analysis may yield biased estimates. Funding None. Research context Evidence before this Type growing public health issue, affecting least half billion people globally. Modifiable factors such physical activity closely related trait inversely diabetes, declining, particularly among youth. Since these traits track youth into early-life interventions might have important implications prevention. However, previous studies typically focused middle-aged individuals, leaving gaps understanding long-term. Moreover, not been designed adequately account confounders. Triangulating evidence across different methods, using sibling comparison would be obtain more accurate reliable estimates causal relationship. Added value nationwide encompassing than million young substantially developing up five decades later. appeared without overweight. While replicated magnitude attenuated an amount relevant. For example, differences deciles about 40% smaller sibling-comparison analyses preventable share hypothetical population-level reduced one-third. Implications available Adolescent strong both These findings render support large-scale surveillance prevention perspective, if confirmed other lines targeting age. Yet, also highlight triangulation obtaining association, shed light pitfalls

Language: Английский

---