epidermal-growth-factor and Cardiovascular-Diseases

Interfering with angiogenesis is an effective, widely used approach to cancer therapy, but antiangiogenic therapies have been associated with important systemic cardiovascular toxicities such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction. As the use of vascular endothelial growth factor signaling pathway (VSP) inhibitors broadens to include older patients and those with existing cardiovascular disease, the adverse effects are likely to be more frequent, and cardiologists will increasingly be enlisted to help oncologists manage patients who develop adverse cardiovascular effects.. The Cardiovascular Toxicities Panel of the National Cancer Institute reviewed the published literature and abstracts from major meetings, shared experience gained during clinical development of VSP inhibitors, and contributed extensive clinical experience in evaluating and treating patients with cancer with cardiovascular disease. This report was edited and approved by the National Cancer Institute Investigational Drug Steering Committee. It presents the panel's expert opinion on the current clinical use and future investigation for safer, more expansive use of these drugs.. The panel recommends that physicians (1) conduct and document a formal risk assessment for existing cardiovascular disease and potential cardiovascular complications before VSP inhibitor treatment recognizing that preexisting hypertension and cardiovascular disease are common in patients with cancer, (2) actively monitor for blood pressure elevations and cardiac toxicity with more frequent assessments during the first treatment cycle, and (3) aggressively manage blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications of VSP inhibitor therapy.

Topics: Antineoplastic Agents; Cardiovascular Diseases; Cardiovascular System; Disease Management; Epidermal Growth Factor; Global Health; Humans; Incidence; Neoplasms; Risk Factors; Signal Transduction

We report the case of a 63-year-old obese man with a rapid-onset of widespread acanthosis nigricans (AN) in the setting of having recently initiated treatment with niacin for dyslipidemia. Although obesity and insulin-resistance are risk factors for AN, AN associated with endocrine dysfunction tends to have a more gradual onset and limited involvement. Owing to our patient's age, the rapid onset, and extensive distribution of his eruption, we initially were concerned about paraneoplastic AN. However, an evaluation for a malignant condition was negative. The timing of the onset of our patient's eruption within several months of starting niacin therapy is consistent with niacin-induced AN. Niacin is known to cause rapidly progressive, widespread AN that is reversible upon discontinuation of the medication. We discuss the pathogenesis of AN, which is thought to be the final common manifestation of stimulation of different subtypes of tyrosine kinase receptors by various epidermal growth factors.

Topics: Acanthosis Nigricans; Cardiovascular Diseases; Diagnosis, Differential; Dyslipidemias; Epidermal Growth Factor; Humans; Hyperinsulinism; Hypolipidemic Agents; Insulin Resistance; Male; Middle Aged; Niacin; Obesity; Paraneoplastic Syndromes; Receptor Protein-Tyrosine Kinases

Although the use of stem cells in cell-replacement therapies by transplantation is obvious, another equally important and interesting application of stem cells is to use them in disease modeling. Disease models serve as a platform to dissect the biochemical mechanisms of normal phenotypes and the processes which go awry during disease conditions. Particularly in complex, multigenic diseases, molecular studies lead to a greater understanding of the disease, and perhaps more targeted approaches for therapies. Stem cells provide an ideal in vitro system in which to study events related to development at the molecular and cellular level. Neural stem cells have been used as excellent models to study the mechanisms of differentiation of cells of the central nervous system. These studies may be particularly relevant to diseases of complex etiology such as psychiatric illnesses, neurodegenerative diseases and brain tumors. Stem cell-derived systems are also being developed to create models of cardiovascular disease. The application of stem cells to the study of cardiovascular illnesses, and vertebrate heart development, is discussed.

Topics: Animals; Autistic Disorder; Brain Neoplasms; Cardiovascular Diseases; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Central Nervous System; Epidermal Growth Factor; Fibroblast Growth Factor 2; Heart; Humans; Mice; Models, Biological; Neoplastic Stem Cells; Neurodegenerative Diseases; Rats; STAT Transcription Factors; Stem Cells; Wnt Proteins

Adipocytes have recently been shown to secrete a variety of bioactive substances called 'adipocytokines', and have been recognized as endocrine cells. Tumour necrosis factor (TNF)-alphaalpha, plasminogen activator inhibitor-1 (PAI-1) and heparin-binding epidermal-growth-factor-like growth factor (HBEGF) are among these adipocytokines, and they contribute to the development of vascular diseases. Visfatin is a visceral fat-specific protein that may be related to the development of obesity-related diseases such as diabetes mellitus and cardiovascular disease. In contrast, adiponectin, an adipose-tissue-specific collagen-like protein, has recently been reported as an important anti-atherogenic and anti-diabetic protein. Adipocytokine secretion may be regulated dynamically by the nutritional state. Visceral fat accumulation leads to dysfunction of adipocytes (including hypersecretion of TNF-alphaalpha, PAI-1 and HBEGF, and hyposecretion of adiponectin), which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, including adiponectin, is discussed with respect to cardiovascular disease.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Cardiovascular Diseases; Cytokines; Epidermal Growth Factor; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Intra-Abdominal Fat; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Tumor Necrosis Factor-alpha

Heparin-binding EGF-like growth factor (HB-EGF) exists as a membrane-anchored form (proHB-EGF) and as its soluble cleaved product (sHB-EGF). The conversion (ectodomain shedding) of proHB-EGF to sHB-EGF is tightly regulated by specific metalloproteinases. Ectodomain shedding plays a central role in GPCR-mediated EGFR transactivation. Antagonizing metalloproteinases can inhibit EGFR transactivation and might be of therapeutic value, for example in cardiac hypertrophy, skin remodeling and tumor growth.

Topics: Animals; Cardiovascular Diseases; Epidermal Growth Factor; Heparin-binding EGF-like Growth Factor; Intercellular Signaling Peptides and Proteins; Liver Regeneration; Metalloendopeptidases; Wound Healing

Urine biomarkers of kidney tubule injury associate with incident hypertension in older adults with comorbidities, but less is known about these associations in younger adults.. In 1170 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults; mean age, 45 years; 40% Black people; 56% women) without hypertension, cardiovascular disease, or kidney disease at baseline, we examined associations of urine MCP-1 (monocyte chemoattractant protein-1), α1m (alpha-1-microglobulin), KIM-1 (kidney injury molecule-1), EGF (epidermal growth factor), IL (interleukin)-18, YKL-40 (chitinase-3-like protein 1), and UMOD (uromodulin) with incident hypertension (onset of systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg or initiation of hypertension medications) and longitudinal BP change in models adjusted for hypertension risk factors, estimated glomerular filtration rate, and albuminuria.. After a median 9.9 (interquartile range, 5.9-10.2) years, 376 participants developed incident hypertension. In demographic-adjusted analyses, higher tertiles of EGF associated with lower risk of incident hypertension in both Black and White participants. After multivariable adjustment, the risk of incident hypertension remained lower in tertile 2 (hazard ratio, 0.70 [95% CI, 0.50-0.97]) and tertile 3 (hazard ratio, 0.58 [0.39-0.85]) of EGF versus tertile 1. In fully adjusted models, participants in EGF tertile 3 had smaller 10-year increases in systolic (-3.4 [95% CI, -6.1 to -0.7] mm Hg) and diastolic BP (-2.6 [95% CI, -4.6 to -0.6] mm Hg) than tertile 1. Other biomarkers showed inconsistent associations with incident hypertension and BP change.. In middle-aged adults without hypertension, cardiovascular disease, or kidney disease, higher urine EGF associated with lower risk of incident hypertension and lower 10-year BP elevations.

Topics: Aged; Biomarkers; Blood Pressure; Cardiovascular Diseases; Epidermal Growth Factor; Female; Glomerular Filtration Rate; Humans; Hypertension; Hypotension; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Risk Factors; Young Adult

Underlying molecular mechanisms of the kidney protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors are not fully elucidated. Therefore, we studied the association between urinary epidermal growth factor (uEGF), a mitogenic factor involved in kidney repair, and kidney outcomes in patients with type 2 diabetes (T2D). The underlying molecular mechanisms of the SGLT2 inhibitor canagliflozin on EGF using single-cell RNA sequencing from kidney tissue were examined. Urinary EGF-to-creatinine ratio (uEGF/Cr) was measured in 3521 CANagliflozin cardioVascular Assessment Study (CANVAS) participants at baseline and week 52. Associations of uEGF/Cr with kidney outcome were assessed using multivariable-adjusted Cox regression models. Single-cell RNA sequencing was performed using protocol kidney biopsy tissue from ten young patients with T2D on SGLT2i, six patients with T2D on standard care only, and six healthy controls (HCs). In CANVAS, each doubling in baseline uEGF/Cr was associated with a 12% (95% confidence interval 1-22) decreased risk of kidney outcome. uEGF/Cr decreased after 52 weeks with placebo and remained stable with canagliflozin (between-group difference +7.3% (2.0-12.8). In young persons with T2D, EGF mRNA was primarily expressed in the thick ascending loop of Henle. Expression in biopsies from T2D without SGLT2i was significantly lower compared to HCs, whereas treatment with SGLT2i increased EGF levels closer to the healthy state. In young persons with T2D without SGLT2i, endothelin-1 emerged as a key regulator of the EGF co-expression network. SGLT2i treatment was associated with a shift towards normal EGF expression. Thus, decreased uEGF represents increased risk of kidney disease progression in patients with T2D. Canagliflozin increased kidney tissue expression of EGF and was associated with a downstream signaling cascade linked to tubular repair and reversal of tubular injury.

Topics: Canagliflozin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Epidermal Growth Factor; Glucose; Humans; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

Cardiovascular adverse complications represent a risk factor for increased cardiovascular morbidity and mortality in patients with major depressive disorder (MDD). However, there is little knowledge of adolescent MDD. We aimed to study complex cardiovascular autonomic regulation and early atherosclerotic damage with a focus on an analysis of heart rate variability (HRV), blood pressure variability (BPV), systolic time intervals, and measures of early atherosclerotic changes in adolescent MDD. Ninety depressive adolescents (34 boys, age 15.8 ± 1.3 yrs.) and 90 age-/gender-matched controls were examined. Evaluated parameters: HRV - time and spectral parameters, BPV - mean, systolic, and diastolic blood pressure, spectral systolic parameters; haemodynamic indices - stroke volume, cardiac output, total peripheral resistance, systolic time intervals - left ventricular ejection time, pre-ejection period; atherosclerotic indices - ankle-brachial index (ABI), pulse wave velocity, brachial-ankle pulse wave velocity, cardio-ankle vascular index; growth factors - epidermal growth factor (EGF), vascular endothelial growth factor associated with monocyte chemoattractant protein-1. Our results showed that the MDD group had significantly reduced HRV and higher BPV measures, shortened systolic time intervals, lower ABI, and higher EGF compared to controls. Concluding, our study revealed that adolescent MDD is associated with cardiovascular dysregulation and early vasculature dysfunction as preclinical markers of higher risk for cardiovascular morbidity, thus adolescence seems to represent an important age period for early diagnosis and prevention of later MDD-linked cardiovascular diseases manifesting in adulthood.

Topics: Adolescent; Adult; Ankle Brachial Index; Blood Pressure; Cardiovascular Diseases; Chemokine CCL2; Depressive Disorder, Major; Epidermal Growth Factor; Heart Rate; Humans; Male; Pulse Wave Analysis; Vascular Endothelial Growth Factor A

To assess changes in metabolic risk factors and cancer-related growth factors associated with short-term abstinence from alcohol.. Prospective, observational study.. Single tertiary centre.. Healthy subjects were recruited based on intention to: (1) abstain from alcohol for 1 month (abstinence group), or (2) continue to drink alcohol (control group). Inclusion criteria were baseline alcohol consumption >64 g/week (men) or >48 g/week (women). Exclusion criteria were known liver disease or alcohol dependence.. The primary outcome was change in insulin resistance (homeostatic model assessment (HOMA) score). Secondary outcomes were changes in weight, blood pressure (BP), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and liver function tests. Primary and secondary outcomes were adjusted for changes in diet, exercise and cigarette smoking.. The abstinence group comprised 94 participants (mean age 45.5 years, SD ±1.2) and the control group 47 participants (mean age 48.7 years, SD ±1.8). Baseline alcohol consumption in the abstinence group was 258.2 g/week, SD ±9.4, and in the control group 233.8 g, SD ±19.0. Significant reductions from baseline in the abstinence group (all p<0.001) were found in: HOMA score (-25.9%, IQR -48.6% to +0.3%), systolic BP (-6.6%, IQR -11.8% to 0.0%), diastolic BP (-6.3%, IQR -14.1% to +1.3%), weight (-1.5%, IQR -2.9% to -0.4%), VEGF (-41.8%, IQR -64.9% to -17.9%) and EGF (-73.9%, IQR -86.1% to -36.4%). None of these changes were associated with changes in diet, exercise or cigarette smoking. No significant changes from baseline in primary or secondary outcomes were noted in the control group.. These findings demonstrate that abstinence from alcohol in moderate-heavy drinkers improves insulin resistance, weight, BP and cancer-related growth factors. These data support an independent association of alcohol consumption with cancer risk, and suggest an increased risk of metabolic diseases such as type 2 diabetes and fatty liver disease.

Topics: Adult; Alcohol Drinking; Alcoholism; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Epidermal Growth Factor; Ethanol; Fatty Liver; Female; Humans; Insulin Resistance; Liver; Liver Function Tests; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Vascular Endothelial Growth Factor A

Increased monocyte chemoattractant protein-1 (MCP-1) and decreased epidermal growth factor (EGF) are promising biomarkers to predict progressive decline in kidney function in non-diabetic kidney diseases. We aimed to evaluate the performance of urinary EGF, MCP-1 or their ratio in predicting rapid decline of GFR in a cohort of Type 2 diabetic patients (T2DM) with diabetic kidney disease (DKD).. T2DM patients (n = 83) with DKD at high risk for renal progression were followed up prospectively. The baseline urine values of MCP-1 to creatinine ratio (UMCP-1), EGF to creatinine ratio (UEGF), EGF to MCP-1 ratio (UEGF/MCP-1) and albumin to creatinine ratio (UACR) were measured. The primary outcome was a decline in estimated glomerular filtration rate (GFR) of ≥25% yearly from baseline.. During follow-up time of 23 months, patients with rapid decline in estimated GFR of ≥25% yearly from baseline had significantly higher baseline levels of UMCP-1, and UACR and lower UEGF and UEGF/MCP-1 ratio. All renal biomarkers predicted primary outcomes with ROC (95%CI) for UMCP-1=0.73 (0.62-0.84), UEGF=0.68 (0.57-0.80), UEGF/MCP-1=0.74 (0.63-0.85), and UACR =0.84 (0.75-0.93). By univariate analysis, blood pressure, GFR, UACR, UMCP-1, UEGF, and UEGF/MCP-1 were associated with rapid decline GFR. By multivariate analysis, UACR, systolic blood pressure, and UMCP-1 or UEGF/MCP-1 were independently associated with rapid GFR decline.. UMCP-1 or UEGF/MCP-1 ratio were associated with rapid renal progression independent from conventional risk factors in DKD.

Topics: Aged; Albuminuria; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Disease Progression; Epidermal Growth Factor; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Prospective Studies; Risk Factors

Epidermal growth factor (EGF) has widespread effects on the developing and mature nervous system. This study examined whether genetic differences in the EGF predict differences in the self-reported level of activity temperament in adults.. Two hundred and ninety-two men and women from the population-based Cardiovascular Risk in Young Finns Study were genotyped for the functional EGF gene A61G polymorphisms, and their temperamental activity was assessed 3 times in 1992, 1997 and 2001.. The EGF gene predicted temperamental activity (the mean of 3 assessments, p = 0.007), with the G/G genotype being associated with the highest level of activity. Additional analyses in separate years indicated that the association was robust across different measurements of activity (p < or = 0.05 in 1992 and 1997, p = 0.008 in 2001).. These results suggest that polymorphic variation in the EGF A61 gene may be one of the factors underlying the temperament dimension of activity.

Topics: Adult; Cardiovascular Diseases; Epidermal Growth Factor; Female; Finland; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Male; Polymorphism, Single Nucleotide; Retrospective Studies; Temperament

Topics: Cardiovascular Diseases; Epidermal Growth Factor; Gene Transfer Techniques; Genetic Therapy; Humans