scholarly journals Phytosterol Accumulation Results in Ventricular Arrhythmia, Impaired Cardiac Function and Death

2021 ◽  
Author(s):  
Hongfei Ge ◽  
Gongxin Liu ◽  
Tracy M. Yamawaki ◽  
Caroline Tao ◽  
Shawn T. Alexander ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cardiac Function ◽  
Cardiac Arrhythmias ◽  
Cardiac Fibrosis ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Pathophysiological Mechanism ◽  
Premature Ventricular Contractions ◽  
Increased Risk ◽  
Impaired Cardiac Function

Abstract Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Both pharmacological and genetic inhibition of phytosterol absorption prevented the induction of both pathways. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These phytosterolemia-associated comorbidities provide novel insight into the underlying pathophysiological mechanism that predispose these patients to increased risk of sudden cardiac death.

scholarly journals Phytosterol accumulation results in ventricular arrhythmia, impaired cardiac function and death in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongfei Ge ◽  
Gongxin Liu ◽  
Tracy M. Yamawaki ◽  
Caroline Tao ◽  
Shawn T. Alexander ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cardiac Function ◽  
Cardiac Arrhythmias ◽  
Cardiac Fibrosis ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiac Injury ◽  
Pathophysiological Mechanism ◽  
Premature Ventricular Contractions ◽  
Impaired Cardiac Function

AbstractHeart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Blockade of phytosterol absorption either by therapeutic inhibition or by genetic inactivation of NPC1L1 prevented the induction of inflammation and arrhythmogenesis. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These comorbidities provide insight into the underlying pathophysiological mechanism for phytosterolemia-associated risk of sudden cardiac death.

Abstract 269: Miofibroblast Tgf-beta Signaling in a Proteotoxic Mouse Model

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Bidur Bhandary ◽  
Qinghang Meng ◽  
Hanna Osinska ◽  
Kritton Shay-Winkler ◽  
James Gulick ◽  
...  
Keyword(s):  
Heart Disease ◽  
Mouse Model ◽  
Cardiac Function ◽  
Transforming Growth Factor Beta ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Prolonged Survival ◽  
Tgfβ Signaling ◽  
Specific Expression ◽  
Western Blots

Introduction: Transforming Growth Factor Beta (TGFβ) is an important cytokine in mediating the fibrogenic response and, in particular, cardiac fibrosis. Extensive fibrosis accompanies the cardiac remodeling that occurs during development of the protein conformation-based disease caused by cardiomyocyte-specific expression of a mutant, small, heat shock-like protein and chaperone, aB crystallin (CryABR120G). During the onset of fibrosis, fibroblasts are activated to the so-called “myofibroblast” state and TGFβ binding is thought to mediate an essential signaling pathway underlying this process. Our central hypothesis is that TGFβ signaling processes that result in significant cardiac fibrosis in a mouse model of proteotoxic heart disease are mediated by cardiac fibroblasts, rather than cardiomyocytes. Here, we have partially ablated TGFβ signaling only in cardiac myofibroblasts to observe if cardiac fibrosis is reduced. Aims and Methods: The objective of this study was to understand the contributions of fibroblast-derived TGFβ signaling to the development of cardiac fibrosis in a proteotoxic mouse model that results in significant cardiac fibrosis. To test the hypothesis we partially deleted the myofibroblast specific canonical and non-canonical signaling by crossing CryAB R120G mice with Tgfbr1 or Tgfbr2 floxed mice. The double transgene containing mice were further crossed with activated myofibroblast specific Cre mice in which Cre expression was driven off the periostin promoter. Echocardiography, Masson’s Trichome staining, PCR arrays, IHC and western blots were performed to characterize the fibrotic progression in CryAB R120G transgenic mice. Results: We observed that myofibroblast-targeted partial knockdown of Tgf βr1 signaling prolonged survival, modestly reducing fibrosis and improving cardiac function . Similarly, Tgf βr2 partial knockdown prolonged survival, modestly reducing fibrosis without improving cardiac function during fibrosis development in CryAB R120G mice. Conclusion: These findings suggest that, in a model of proteotoxic heart disease, myofibroblast based TGFβ signaling in the heart may contribute to cardiac hypertrophy/dysfunction but cannot account entirely for the fibrotic response.

Abstract MP74: Long Term Risk-Factor Profiles for Chronic Kidney Disease in the Framingham Heart Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gearoid M McMahon ◽  
Sarah R Preis ◽  
Shih-Jen Hwang ◽  
Caroline S Fox
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Framingham Heart Study ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Standard Deviation Increase ◽  
Heart Study ◽  
Increased Risk

Background: Chronic Kidney Disease (CKD) is an important public health issue and is associated with an increased risk of cardiovascular disease. Risk factors for CKD are well established, but most are typically assessed at or near the time of CKD diagnosis. Our hypothesis was that risk factors for CKD are present earlier in the course of the disease. We compared the prevalence of risk factors between CKD cases and controls at time points up to 30 years prior to CKD diagnosis. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort. CKD was defined as an estimated glomerular filtration rate of ≤60ml/min/1.73m2. Incident CKD cases occurring at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to controls. Risk factors including systolic blood pressure (SBP), hypertension, lipids, diabetes, smoking status, body mass index (BMI) and dipstick proteinuria were measured at the time of CKD diagnosis and 10, 20 and 30 years prior. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls Results: During follow-up, 441 new cases of CKD were identified and these were matched to 882 controls (mean age 69.2 years, 52.4% women). Up to 30 years prior to CKD diagnosis, those who ultimately developed CKD were more likely to have hypertension (OR 1.74, CI 1.21-2.49), be obese (OR 1.74, CI 1.15-2.63) and have higher triglycerides (OR 1.43, CI 1.12-1.84, p=0.005 per 1 standard deviation increase). Each 10mmHg increase in SBP was associated with an OR of 1.22 for future CKD (95% CI 1.10-1.35) Additionally, cases were more likely to have diabetes (OR 2.90, CI 1.59-5.29) and be on antihypertensive therapy (OR 1.65, CI 1.14-2.40, p=0.009) up to 20 years prior to diagnosis. Increasing HDLc was associated with a lower risk of CKD (OR 0.84, CI 0.81-0.97 per 10mg/dl). Conclusions: As many as 30 years prior to diagnosis, risk factors for CKD are identifiable. In particular, modifiable risk factors such as obesity, hypertension and dyslipidemia are present early in the course of the disease. These findings demonstrate the importance of early identification of risk factors in patients at risk of CKD through a life-course approach.

Abstract P087: Association of Psychological Well-Being With Cardiac Repolarization

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Amit J Shah ◽  
Robert Carney ◽  
Elsayed Z Soliman ◽  
Viola Vaccarino
Keyword(s):  
Psychological Health ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Well Being ◽  
Left Ventricular ◽  
Morbidity And Mortality ◽  
Psychological Well Being ◽  
Psychological Wellness ◽  
Increased Risk ◽  
The Mean

Background: Abnormal frontal T-axis is an independent predictor of mortality, and may be influenced by increased sympathetic tone and cardiovascular disease risk factors. Factors related to poor psychological health, such as depression, are associated with increased risk of CVD morbidity, although the mechanisms are not clear. We tested the hypothesis that: 1) reduced psychological wellness is associated with abnormal T-axis and 2) this association may help to explain the excess risk of CVD morbidity and mortality related to poor psychological health. Methods: We studied 4485 community-based adults aged 25–65 years without a history of CVD from NHANES I (1971–75) who were monitored for CVD hospitalization and death until 1993. Those with ECG evidence of previous MI, left ventricular hypertrophy, and major ventricular conduction defects (QRS interval ≥ 120 ms) were excluded. Frontal T-axis was obtained through 12-lead ECG, and a deviation of ≥ 30° from normal (45°) was considered abnormal. Psychological well-being was measured with the General Well-Being Scale (GWB). Results: The mean ± SD age was 43.1 ± 11.5 years and 55% were women. The mean ± SD GWB score was 80.5 ± 17.3, the median frontal T-axis was 51°, and 13% had an abnormal T-axis. In cross-sectional analysis adjusting for age, sex, and race, a 1-SD decrease in GWB was associated with an OR of 1.12 for abnormal T-axis (p=0.01). This effect was unchanged after adjusting for systolic blood pressure, smoking, diabetes, total cholesterol, and BMI. Abnormal T-axis was associated with CVD hospitalization/death (adjusted HR 1.29, p=0.01), as was GWB (adjusted HR 1.104 per 1-SD decrease, p=0.01). When both factors were included in the model, the HR of GWB decreased by 8% to 1.096 (p=0.02). Conclusion: Abnormal frontal T-axis is modestly but significantly associated with reduced psychological wellness. Although this association may help understand neurocardiac relationships, it does not substantially explain morbidity and mortality associated with reduced psychological wellness.

scholarly journals Plasma Dehydroepiandrosterone Sulfate and Cardiovascular Disease Risk in Older Men and Women

2020 ◽  
Vol 105 (12) ◽  
pp. e4304-e4327 ◽  
Author(s):  
Xiaoming Jia ◽  
Caroline Sun ◽  
Olive Tang ◽  
Ivan Gorlov ◽  
Vijay Nambi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Dehydroepiandrosterone Sulfate ◽  
Mortality Data ◽  
Atherosclerosis Risk In Communities ◽  
Percentage Decrease ◽  
Increased Risk ◽  
Study Population

Abstract Context Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events. Objective Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults. Design DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events: 18 years for DHEA-S level; 5.5 years for DHEA-S change. Setting General community. Participants Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years). Main Outcome Measure Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events. Results DHEA-S below the 15th sex-specific percentile of the study population (men: 55.4 µg/dL; women: 27.4 µg/dL) was associated with increased HF hospitalization (men: hazard ratio [HR] 1.30, 95% confidence interval [CI], 1.07-1.58; women: HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men: 70.0 µg/dL; women: 37.1 µg/dL) was associated with increased death (men: HR 1.12, 95% CI, 1.01-1.25; women: HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD. Conclusions Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.

scholarly journals Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1653
Author(s):  
Sze Wa Chan ◽  
Brian Tomlinson
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Vision Loss ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiovascular Complications ◽  
Increased Risk ◽  
Potential Benefits

Metabolic syndrome is a cluster of interrelated conditions that is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Oxidative stress may impair normal physiological functions, leading to various illnesses. T2DM is considered to be associated with increased oxidative stress, inflammation, and dyslipidemia, which may play a significant role in the development of cardiovascular complications, cancer and vision loss through cataracts and retinopathy. While conventional therapies are a cornerstone for the management of the major risk factors of metabolic syndrome, increasing antioxidant defense by increasing intake of antioxidant-rich foods may improve long term prospects in CVD, obesity and T2DM. Bilberry (Vaccinium myrtillus L.) is one of the richest natural sources of anthocyanins which give berries their red/purple/blue coloration. Anthocyanins are powerful antioxidants and are reported to play an important role in the prevention of metabolic disease and CVD as well as cancer and other conditions. This review focuses on the potential effects of bilberry supplementation on metabolic and cardiovascular risk factors. Although there is evidence to support the use of bilberry supplementation as part of a healthy diet, the potential benefits from the use of bilberry supplementation in patients with T2DM or CVD needs to be clarified in large clinical trials.

scholarly journals Accelerated metabolic susceptibility to type 2 diabetes in older women with a history of gestational diabetes

2013 ◽  
Vol 2 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Alice S Ryan ◽  
John C McLenithan ◽  
Gretchen M Zietowski
Keyword(s):  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Postmenopausal Women ◽  
Central Obesity ◽  
Glucose Utilization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Increased Risk ◽  
History Of

The purpose of this study is to compare central obesity, insulin sensitivity, and cardiovascular disease risk factors between premenopausal and postmenopausal women with a history of gestational diabetes mellitus (GDM), controls, and women with type 2 diabetes (T2DM). Subjects were 73 overweight/obese and sedentary women who had a history of GDM (n=31) and were either premenopausal (n=11, 44±1 years, X±s.e.m.), postmenopausal (n=20, 58±1 years), or without a history of GDM as healthy postmenopausal controls (n=27, 57±1 years) or postmenopausal with T2DM (n=16, 59±1 years). The premenopausal GDM women had higher maximal oxygen uptake and lower visceral fat than the other three groups (P<0.05). BMI, %body fat, subcutaneous abdominal fat, and intramuscular fat did not differ significantly among the four groups. Glucose utilization (M, 3 h 40 mU/m2 per min hyperinsulinemic–euglycemic clamps) was 27% higher (P=0.05) in pre- than postmenopausal GDM and was not different between premenopausal GDM and postmenopausal controls. M was 28% lower (P=0.06) in postmenopausal GDM than controls and was not significantly different between postmenopausal GDM and T2DM groups. Thus, despite being younger and more physically fit, premenopausal women with prior GDM display similar central obesity, glucose, and metabolic profiles as postmenopausal controls. Postmenopausal women with prior GDM are more insulin resistant than controls of similar age, adiposity, and fitness levels and display comparable glucose utilization rates as similar as women with T2DM suggesting that a prior history of GDM may be an early manifestation of increased risk of later T2DM.

scholarly journals Novel Cardiovascular Biomarkers Associated with Increased Cardiovascular Risk in Women With Prior Preeclampsia/HELLP Syndrome: A Narrative Review

2021 ◽  
Vol 16 ◽  
Author(s):  
Esmee ME Bovee ◽  
Martha Gulati ◽  
Angela HEM Maas
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Hellp Syndrome ◽  
Troponin I ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Narrative Review ◽  
Elevated Liver Enzymes ◽  
Increased Risk ◽  
Cardiovascular Biomarkers

Evidence has shown that women with a history of preeclampsia or haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome have an increased risk of cardiovascular disease later in life. Recommendations for screening, prevention and management after such pregnancies are not yet defined. The identification of promising non-traditional cardiovascular biomarkers might be useful to predict which women are at greatest risk. Many studies are inconsistent and an overview of the most promising biomarkers is currently lacking. This narrative review provides an update of the current literature on circulating cardiovascular biomarkers that may be associated with an increased cardiovascular disease risk in women after previous preeclampsia/HELLP syndrome. Fifty-six studies on 53 biomarkers were included. From the summary of evidence, soluble fms-like tyrosine kinase-1, placental growth factor, interleukin (IL)-6, IL-6/IL-10 ratio, high-sensitivity cardiac troponin I, activin A, soluble human leukocyte antigen G, pregnancy-associated plasma protein A and norepinephrine show potential and are interesting candidate biomarkers to further explore. These biomarkers might be potentially eligible for cardiovascular risk stratification after preeclampsia/HELLP syndrome and may contribute to the development of adequate strategies for prevention of hypertension and adverse events in this population.

scholarly journals Obesity-Related Metabolic Dysfunction in Dairy Cows and Horses: Comparison to Human Metabolic Syndrome

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1406
Author(s):  
Zsofia Daradics ◽  
Cristian M. Crecan ◽  
Mirela A. Rus ◽  
Iancu A. Morar ◽  
Mircea V. Mircean ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Dairy Cows ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Clinical Consequence ◽  
Atherosclerotic Cardiovascular Disease ◽  
Metabolic Dysfunction ◽  
Housing Systems ◽  
Animal Populations ◽  
Increased Risk

Obesity has become a serious health problem with frequent occurrence both in human and animal populations. It is estimated that it may affect over 85% of the human population and 70–80% of horses and cows by 2030. Fat cow syndrome (FCS) is a combination of metabolic, digestive, infectious, and reproductive disorders that affects obese periparturient dairy cows, and occurs most frequently in loose-housing systems, where periparturient and dry cows are fed and managed in one group disregarding the lactation stages. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS) and has insulin dysregulation as a central and consistent feature. It is often associated with obesity, although EMS may occur in a lean phenotype as well. Other inconsistent features of EMS are cardiovascular changes and adipose dysregulation. Laminitis is the main clinical consequence of EMS. MetS holds a 30-years old lead in research and represents a clustering of risk factors that comprise abdominal obesity, dyslipidemia, hypertension, and hyperglycemia (impaired fasting glucose or type 2 diabetes mellitus—T2DM), which are associated with doubled atherosclerotic cardiovascular disease risk, and a 5-fold increased risk for T2DM. The main aim of this review is to provide critical information for better understanding of the underlying mechanisms of obesity-related metabolic dysfunction in animals, especially in cows and horses, in comparison with MetS. Human medicine studies can offer suitable candidate mechanisms to fill the existing gap in the literature, which might be indispensable for owners to tackle FCS, EMS, and their consequences.

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