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1.
AJR Am J Roentgenol ; 219(3): 407-419, 2022 09.
Article in English | MEDLINE | ID: mdl-35441530

ABSTRACT

BACKGROUND. Deep learning frameworks have been applied to interpretation of coronary CTA performed for coronary artery disease (CAD) evaluation. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of myocardial perfusion imaging (MPI) and coronary CTA with artificial intelligence quantitative CT (AI-QCT) interpretation for detection of obstructive CAD on invasive angiography and to assess the downstream impact of including coronary CTA with AI-QCT in diagnostic algorithms. METHODS. This study entailed a retrospective post hoc analysis of the derivation cohort of the prospective 23-center Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) trial. The study included 301 patients (88 women and 213 men; mean age, 64.4 ± 10.2 [SD] years) recruited from May 2014 to May 2017 with stable symptoms of myocardial ischemia referred for nonemergent invasive angiography. Patients underwent coronary CTA and MPI before angiography with quantitative coronary angiography (QCA) measurements and fractional flow reserve (FFR). CTA examinations were analyzed using an FDA-cleared cloud-based software platform that performs AI-QCT for stenosis determination. Diagnostic performance was evaluated. Diagnostic algorithms were compared. RESULTS. Among 102 patients with no ischemia on MPI, AI-QCT identified obstructive (≥ 50%) stenosis in 54% of patients, including severe (≥ 70%) stenosis in 20%. Among 199 patients with ischemia on MPI, AI-QCT identified nonobstructive (1-49%) stenosis in 23%. AI-QCT had significantly higher AUC (all p < .001) than MPI for predicting ≥ 50% stenosis by QCA (0.88 vs 0.66), ≥ 70% stenosis by QCA (0.92 vs 0.81), and FFR < 0.80 (0.90 vs 0.71). An AI-QCT result of ≥ 50% stenosis and ischemia on stress MPI had sensitivity of 95% versus 74% and specificity of 63% versus 43% for detecting ≥ 50% stenosis by QCA measurement. Compared with performing MPI in all patients and those showing ischemia undergoing invasive angiography, a scenario of performing coronary CTA with AIQCT in all patients and those showing ≥ 70% stenosis undergoing invasive angiography would reduce invasive angiography utilization by 39%; a scenario of performing MPI in all patients and those showing ischemia undergoing coronary CTA with AI-QCT and those with ≥ 70% stenosis on AI-QCT undergoing invasive angiography would reduce invasive angiography utilization by 49%. CONCLUSION. Coronary CTA with AI-QCT had higher diagnostic performance than MPI for detecting obstructive CAD. CLINICAL IMPACT. A diagnostic algorithm incorporating AI-QCT could substantially reduce unnecessary downstream invasive testing and costs. TRIAL REGISTRATION. Clinicaltrials.gov NCT02173275.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Myocardial Ischemia , Myocardial Perfusion Imaging , Aged , Artificial Intelligence , Computed Tomography Angiography/methods , Constriction, Pathologic , Coronary Angiography/methods , Coronary Stenosis/diagnostic imaging , Female , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Predictive Value of Tests , Prospective Studies , Reference Standards , Retrospective Studies
2.
Catheter Cardiovasc Interv ; 97(6): E887-E892, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33175473

ABSTRACT

Transcatheter mitral valve replacement (TMVR) is an exciting alternative therapy for complex patients with mitral valve disease. Experience with TMVR is new and there is a lot yet to discover about their durability, long-term outcomes, and complications including mitral transcatheter heart valve (THV) thrombosis. Many factors have been speculated to increased risk of THV thrombosis. Here, we report a case of a 72-year-old woman who developed mitral THV thrombosis after undergoing TMVR for severe mitral regurgitation with mitral annular calcification. We reviewed 42 TMVR papers with 1,484 patients, including 60 with mitral THV thrombosis. We discussed the most common strategies used for mitral THV thromboprophylaxis and treatment.


Subject(s)
Heart Valve Prosthesis Implantation , Thrombosis , Venous Thromboembolism , Aged , Anticoagulants , Cardiac Catheterization/adverse effects , Female , Heart Valve Prosthesis Implantation/adverse effects , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Thrombosis/diagnostic imaging , Thrombosis/etiology , Treatment Outcome
3.
Ann Noninvasive Electrocardiol ; 19(6): 552-60, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24750238

ABSTRACT

BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) is a known predictor of poor cardiovascular outcomes. Although ECG LV hypertrophy (LVH) is strongly associated with LV systolic dysfunction and heart failure, the relation of LV DD to ECG LVH is unclear. METHODS: ECG LVH by Cornell product (CP) criteria was examined in a cohort of 185 patients who underwent both cardiac computed tomographic angiography and transthoracic echocardiography with complete evaluation of diastolic function. The presence of DD was determined via evaluation of mitral inflow velocities, tissue Doppler imaging, deceleration time, isovolumic relaxation time, pulmonary venous systolic: diastolic ratio, and left atrial enlargement. RESULTS: Among the 185 patients (56% female, mean age 54.6 ± 15.6), 105 (57%) had DD. In univariate logistic regression analysis, patients in the upper quartile of CP (≥1595 mm·ms) had a >5-fold greater odds of DD (odds ratio [OR] 5.1, 95% confidence interval [CI] 2.2-11.7, P < 0.001). In alternative analyses treating CP as a continuous variable, each 1 SD increase in CP (664 mm·ms) was associated with an OR of 1.9 for DD (95% CI 1.3-2.7, P < 0.001). In multivariate logistic regression analyses adjusting for univariate predictors of DD, the highest quartile of CP remained associated with a 5.9-fold increased odds of DD (95% CI 2.3-15.4, P = 0.001), and each 1 SD of CP with a 1.7-fold increased odds of DD (95% CI 1.2-2.5, P = 0.005). CONCLUSIONS: CP LVH is a strong predictor of DD, even after adjustment for other potential risk factors and ECG variables.


Subject(s)
Diastole/physiology , Electrocardiography/methods , Hypertrophy, Left Ventricular/complications , Hypertrophy, Left Ventricular/physiopathology , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/physiopathology , Cohort Studies , Echocardiography, Doppler/methods , Female , Humans , Male , Middle Aged , Odds Ratio , Risk Factors , Tomography, X-Ray Computed/methods , Ventricular Dysfunction, Left/diagnosis
4.
J Ultrasound Med ; 32(6): 1003-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23716522

ABSTRACT

OBJECTIVES: Bedside sonography for diagnosis of pneumothorax has been well described in emergency and trauma medicine literature. Its role in detection of iatrogenic pneumothorax has not been well studied. We describe the performance of bedside sonography for detection of procedure-related pneumothorax and highlight some limitations. METHODS: A total of 185 patients underwent thoracentesis (n = 60), transbronchial biopsy (n = 48), and computed tomography-guided needle lung biopsy (n = 77). Bedside preprocedure and postprocedure transthoracic sonography and postprocedure chest radiograph were performed in all patients. Patients in whom the pleural surface was not well imaged with sonography were said to have a limited examination. Chest radiography was the standard for diagnosing pneumothorax. RESULTS: Chest radiography showed pneumothorax in 8 of 185 patients (4.0%). These patients had undergone computed tomography-guided needle lung biopsy (n = 7) and transbronchial needle lung biopsy (n = 1). Sonography showed pneumothorax in 7 of these patients. The sensitivity, specificity, and diagnostic accuracy were 88%, 97%, and 97%, respectively. Limited-quality sonographic examinations due to preexisting lung disease were seen in 43 of 185 patients. The positive and negative likelihood ratios for patients with adequate scans were 55 and 0.17, respectively. The likelihood ratio for patients with limited-quality scans was 1.08. CONCLUSIONS: When a good-quality scan is achieved, bedside chest sonography is a valuable tool for evaluation of postprocedure pneumothorax. Patients with preexisting lung disease, in whom the quality of the sonographic examination is limited, should be studied with chest radiography.


Subject(s)
Biopsy, Needle/statistics & numerical data , Paracentesis/statistics & numerical data , Pneumothorax/diagnostic imaging , Pneumothorax/epidemiology , Point-of-Care Systems/statistics & numerical data , Postoperative Complications/diagnostic imaging , Ultrasonography/statistics & numerical data , Adult , Aged , Aged, 80 and over , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , New York/epidemiology , Observational Studies as Topic , Postoperative Complications/epidemiology , Prevalence , Reproducibility of Results , Risk Assessment , Sensitivity and Specificity , Young Adult
5.
Front Cardiovasc Med ; 9: 839400, 2022.
Article in English | MEDLINE | ID: mdl-35387447

ABSTRACT

Coronary artery disease is a leading cause of death worldwide. There has been a myriad of advancements in the field of cardiovascular imaging to aid in diagnosis, treatment, and prevention of coronary artery disease. The application of artificial intelligence in medicine, particularly in cardiovascular medicine has erupted in the past decade. This article serves to highlight the highest yield articles within cardiovascular imaging with an emphasis on coronary CT angiography methods for % stenosis evaluation and atherosclerosis quantification for the general cardiologist. The paper finally discusses the evolving paradigm of implementation of artificial intelligence in real world practice.

6.
J Invasive Cardiol ; 34(8): E601-E610, 2022 08.
Article in English | MEDLINE | ID: mdl-35830359

ABSTRACT

OBJECTIVES: This study aims to compare veterans and non-veterans undergoing transcatheter aortic valve replacement (TAVR) using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) registry. METHODS: Patients undergoing TAVR at George Washington University (GWU) and veterans treated at Washington DC Veterans Affairs Medical Center (VAMC) who underwent TAVR at GWU from 2014-2020 were included. All patients were reported in the TVT registry. Emergency and valve-in-valve TAVR were excluded. Cohorts were divided based on veteran status. Operators were the same for both groups. Outcomes were compared at 30 days and 1 year. The primary outcome was mortality and secondary outcomes were morbidity metrics. RESULTS: A total of 299 patients (91 veterans, 208 non-veterans) were included. Veterans had higher rates of hypertension (87.9% vs 77.9%; P=.04), diabetes (46.7% vs 28.9%; P<.01), and lung disease (2.4% vs 11.0%; P<.001). Outcomes were not significantly different between veterans and non-veterans, including 30-day mortality (0% vs 2.9%, respectively; P=.18), 1-year mortality (9.8% vs 10.7%, respectively; P=.61), stroke incidence (0% vs 2.5%, respectively; P=.73), median intensive care unit stay (24 hours in both groups), and overall hospital stay (2 days in both groups). CONCLUSIONS: The affiliation between a VAMC and an academic medical center allowed for direct comparison between veterans and non-veterans undergoing TAVR by the same operators using the TVT registry. Despite significantly higher rates of comorbidities, veterans had equivalent outcomes compared with non-veterans. This may be in part due to the comprehensive care that veterans receive in the VAMC and this institution's integrated heart center team.


Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Aortic Valve/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Humans , Registries , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome , United States/epidemiology
7.
Tex Heart Inst J ; 48(3)2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34383956

ABSTRACT

Mitochondrial disease comprises a wide range of genetic disorders caused by mitochondrial dysfunction. Its rarity, however, has limited the ability to assess its effects on clinical outcomes. To evaluate this relationship, we collected data from the 2016 National Inpatient Sample, which includes data from >7 million hospital stays. We identified 705 patients (mean age, 22 ± 20.7 yr; 54.2% female; 67.4% white) whose records included the ICD-10-CM code E88.4. We also identified a propensity-matched cohort of 705 patients without mitochondrial disease to examine the effect of mitochondrial disease on major adverse cardiovascular events, including all-cause in-hospital death, cardiac arrest, and acute congestive heart failure. Patients with mitochondrial disease were at significantly greater risk of major adverse cardiovascular events (odds ratio [OR]=2.42; 95% CI, 1.29-4.57; P=0.005), systolic heart failure (OR=2.37; 95% CI, 1.08-5.22; P=0.027), and all-cause in-hospital death (OR=14.22; 95% CI, 1.87-108.45; P<0.001). These findings suggest that mitochondrial disease significantly increases the risk of inpatient major adverse cardiovascular events.


Subject(s)
Cardiovascular Diseases/epidemiology , Inpatients , Mitochondrial Diseases/complications , Propensity Score , Risk Assessment/methods , Adult , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Incidence , Male , Middle Aged , Mitochondrial Diseases/epidemiology , Risk Factors , Survival Rate/trends , United States , Young Adult
8.
Am J Cardiol ; 144: 143-147, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33385354

ABSTRACT

Approximately one in 3 patients in the United States are obese. There is a strong association between obesity and an increased rate of cardiovascular disease (CVD)-related mortality. Bariatric surgery (BS) has emerged as an effective strategy to achieve reduction of excess weight. Our study aims to explore the relationship between BS and major adverse cardiovascular events (MACE) among obese hospitalized patients in the United States. This is a retrospective study of all obese adult patients with BMI ≥35 kg/m2 (n= 1,700,943) in the National Inpatient Sample between 2012 and 2016. Differences in the clinical characteristics of obese patients with a history of BS versus obese patients without a history of BS were analyzed as well as the association between BS and MACE after adjusting for CVD risk factors. Among 50,296 obese patients with a history of BS (2.96%), the mean age was 53 ± 12 years with the majority being female (75.32%) and Caucasian (71.85%). Multivariate analysis revealed that obese patients with a history of BS had a1.6-fold decrease odds of MACE compared with patients without BS (OR 0.62; 95% CI, 0.60 to 0.65; p <0.001). In conclusion, this study illustrates that among obese patients with BMI ≥35 kg/m2, history of BS was associated with a significantly lower odds of inpatient MACE, after adjusting for CVD risk factors.


Subject(s)
Bariatric Surgery/statistics & numerical data , Heart Arrest/epidemiology , Heart Failure/epidemiology , Hospital Mortality , Hospitalization , Myocardial Infarction/epidemiology , Obesity, Morbid/epidemiology , Stroke/epidemiology , Adult , Aged , Female , Humans , Logistic Models , Male , Middle Aged , Mortality , Multivariate Analysis , Obesity, Morbid/surgery , Protective Factors , Risk Factors , United States/epidemiology
9.
Article in English | MEDLINE | ID: mdl-33746507

ABSTRACT

PURPOSE OF REVIEW: Social media (SoMe) as a means of knowledge dissemination has grown significantly in cardiovascular imaging in recent years. This media platform allows for a free exchange of ideas, the development of new communities, and the ability to disseminate advancements rapidly. While the social media platforms offer limitless potential, their public domain necessitates several important suggestions around best practices. RECENT FINDINGS: In cardiovascular imaging, specific hashtags have emerged to encompass the major modalities to include #EchoFirst, #YesCCT, #WhyCMR, and #CVNuc. Cardiovascular imaging journals have established major presences in the social media space as an avenue to present novel, high-quality, peer-reviewed content to new audiences. SUMMARY: This review paper aims to introduce basic concepts in social media and cardiovascular imaging while highlighting recent topics of high importance, influence, and attention in cardiovascular imaging to include the ISCHEMIA trial, COVID-19, structural imaging, and multimodality advances from throughout 2020.

10.
Circ Cardiovasc Qual Outcomes ; 12(4): e005597, 2019 04.
Article in English | MEDLINE | ID: mdl-30950651

ABSTRACT

BACKGROUND: As of 2016, ≈1.4 million people in the United States identify as transgender. Despite their growing number and increasing specific medical needs, there has been a lack of research on cardiovascular disease (CVD) and CVD risk factors in this population. Recent studies have reported that the transgender population had a significantly higher rate of CVD risk factors without a significant increase in overall CVD morbidity and mortality. These studies are limited by their small sample sizes and their predominant focus on younger transgender populations. With a larger sample size and inclusion of broader age range, our study aims to provide insight into the association between being transgender and cardiovascular risk factors, as well as myocardial infarction. METHODS AND RESULTS: The Behavioral Risk Factor Surveillance System data from 2014 to 2017 were used to evaluate the cross-sectional association between being transgender and the reported history of myocardial infarction and CVD risk factors. A logistic regression model was constructed to study the association between being transgender and myocardial infarction after adjusting for CVD risk factors including age, diabetes mellitus, hypertension, hypercholesterolemia, chronic kidney disease, smoking, and exercise. Multivariable analysis revealed that transgender men had a >2-fold and 4-fold increase in the rate of myocardial infarction compared with cisgender men (odds ratio, 2.53; 95% CI, 1.14-5.63; P=0.02) and cisgender women (odds ratio, 4.90; 95% CI, 2.21-10.90; P<0.01), respectively. Conversely, transgender women had >2-fold increase in the rate of myocardial infarction compared with cisgender women (odds ratio, 2.56; 95% CI, 1.78-3.68; P<0.01) but did not have a significant increase in the rate of myocardial infarction compared with cisgender men. CONCLUSIONS: The transgender population had a higher reported history of myocardial infarction in comparison to the cisgender population, except for transgender women compared with cisgender men, even after adjusting for cardiovascular risk factors.


Subject(s)
Cardiovascular Diseases/epidemiology , Minority Health , Myocardial Infarction/epidemiology , Transgender Persons , Transsexualism/epidemiology , Adult , Aged , Cardiovascular Diseases/diagnosis , Cross-Sectional Studies , Female , Health Surveys , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Prognosis , Risk Assessment , Risk Factors , Sex Factors , Transsexualism/diagnosis , United States/epidemiology
11.
J Cardiovasc Comput Tomogr ; 11(4): 302-308, 2017.
Article in English | MEDLINE | ID: mdl-28457950

ABSTRACT

BACKGROUND: The threshold for the optimal computed tomography (CT) number in Hounsfield Units (HU) to quantify aortic valvular calcium on contrast-enhanced scans has not been standardized. Our aim was to find the most accurate threshold to predict paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR). METHODS: 104 patients who underwent TAVR with the CoreValve prosthesis were studied retrospectively. Luminal attenuation (LA) in HU was measured at the level of the aortic annulus. Calcium volume score for the aortic valvular complex was measured using 6 threshold cutoffs (650 HU, 850 HU, LA × 1.25, LA × 1.5, LA+50, LA+100). Receiver-operating characteristic (ROC) analysis was performed to assess the predictive value for > mild PVR (n = 16). Multivariable analysis was performed to determine the accuracy to predict > mild PVR after adjustment for depth and perimeter oversizing. RESULTS: ROC analysis showed lower area under the curve (AUC) values for fixed threshold cutoffs (650 or 850 HU) compared to thresholds relative to LA. The LA+100 threshold had the highest AUC (0.81), and AUC was higher than all studied protocols, other than the LA x 1.25 and LA + 50 protocols, where the difference approached statistical significance (p = 0.05, and 0.068, respectively). Multivariable analysis showed calcium volume determined by the LAx1.25, LAx1.5, LA+50, and LA+ 100 HU protocols to independently predict PVR. CONCLUSIONS: Calcium volume scoring thresholds which are relative to LA are more predictive of PVR post-TAVR than those which use fixed cutoffs. A threshold of LA+100 HU had the highest predictive value.


Subject(s)
Aortic Valve Insufficiency/etiology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Calcinosis/diagnostic imaging , Contrast Media/administration & dosage , Tomography, X-Ray Computed , Transcatheter Aortic Valve Replacement/adverse effects , Aged , Aged, 80 and over , Aortic Valve/physiopathology , Aortic Valve/surgery , Aortic Valve Insufficiency/physiopathology , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Area Under Curve , Calcinosis/physiopathology , Calcinosis/surgery , Echocardiography, Transesophageal , Female , Heart Valve Prosthesis , Humans , Logistic Models , Male , Multivariate Analysis , Predictive Value of Tests , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Transcatheter Aortic Valve Replacement/instrumentation , Treatment Outcome
12.
Congenit Heart Dis ; 12(6): 740-745, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28805011

ABSTRACT

BACKGROUND: Unicuspid aortic valve (UAV) is a rare disorder, often difficult to distinguish from bicuspid aortic valve (BAV). BAV and UAV share valve pathology such as the presence of a raphe, leaflet fusion, aortic stenosis, aortic regurgitation, and/or ascending aortic dilatation, but a comprehensive echocardiographic comparison of patients with UAV and BAV has not been previously performed. METHODS: We investigated UAV and BAV patients at an early stage of disease included in GenTAC, a national registry of genetically related aortic aneurysms and associated cardiac conditions. Clinical and echocardiographic data from the GenTAC Registry were compared between 17 patients with UAV and 17 matched-controls with BAV. RESULTS: Baseline characteristics including demographics, clinical findings including family history of BAV and aortic aneurysm/coarctation, and echocardiographic variables were similar between BAV and UAV patients; aortic stenosis was more common and more severe in patients with UAV. This was evidenced by higher mean and peak gradient, smaller aortic valve area, and more advanced valvular degeneration (all P < .05). There were no significant differences in aortic dimensions, with a similar pattern of enlargement of the ascending aorta. CONCLUSIONS: The similar baseline characteristics with more accelerated aortic valve degeneration and stenosis suggest that UAV represents an extreme in the spectrum of BAV syndromes. Therefore, it is reasonable to consider application of recommendations for the management of patients with BAV to those with the rarer UAV.


Subject(s)
Aortic Valve/abnormalities , Heart Valve Diseases/genetics , Registries , Adolescent , Adult , Aorta/diagnostic imaging , Aortic Valve/diagnostic imaging , Bicuspid Aortic Valve Disease , Child , Child, Preschool , Diagnosis, Differential , Echocardiography , Female , Heart Valve Diseases/congenital , Heart Valve Diseases/diagnosis , Humans , Infant , Male , Middle Aged , Phenotype , Retrospective Studies , Young Adult
14.
Acute Card Care ; 17(4): 83-84, 2015 Dec.
Article in English | MEDLINE | ID: mdl-27494267

ABSTRACT

The need for cardiovascular expertise in the treatment of advanced heart failure (AHF), malignant arrhythmias, and structural heart disease has shifted the role of the CCU to a more diverse and medically complex patient population. This study's purpose was to analyze the temporal trends in the principal diagnosis leading to admission to the CCU in a tertiary referral hospital. Over the last 15 years, the CCU has evolved from a medical unit strictly focusing on the care of patients with ACS to an advanced cardiac intensive care unit. The trends observed at our center provide further evidence that today's CCU contains a broader, more complex, critically-ill patient population.


Subject(s)
Coronary Care Units/statistics & numerical data , Forecasting , Heart Diseases , Tertiary Care Centers/statistics & numerical data , Urban Health Services/statistics & numerical data , Follow-Up Studies , Heart Diseases/diagnosis , Heart Diseases/mortality , Heart Diseases/therapy , Hospital Mortality/trends , Humans , Morbidity/trends , Patient Admission/statistics & numerical data , Prospective Studies , United States/epidemiology
15.
Int J Parasitol ; 41(5): 533-43, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21172351

ABSTRACT

When hookworm infective L3s infect their mammalian host, they undergo a temperature shift from that of the ambient environment to that of their endothermic host. Additionally, L3s living in the environment can be exposed to temperature extremes associated with weather fluctuations. The heat shock response (HSR) is a conserved response to heat shock and other stress that involves the expression of protective heat shock proteins (HSPs). The HSR is controlled by heat shock factor-1 (HSF-1), a conserved transcription factor that binds to a heat shock element in the promoter of HSPs, causing their expression. HSF-1 is negatively regulated in part by a HSF binding protein (HSB-1) that binds to and removes HSF-1 trimers bound to HSP gene promoters, resulting in attenuation of the HSR. Herein we describe an HSB-1 orthologue, Ac-HSB-1, from the hookworm Ancylostoma caninum. The Ac-hsb-1 cDNA encodes a 79 amino acid protein that is 71% identical to the Caenorhabditis elegans HSB-1, and is predicted to share the characteristic coiled-coil structural motif comprised of two interacting alpha helices. Recombinant Ac-HSB-1 immunoprecipitated Ce-HSF-1 expressed in mammalian cells that had been heat shocked for 1h at 42°C, but not from cells incubated at 37°C, indicating that HSB-1 only bound to the active DNA binding form of HSF-1. Expression of Ac-hsb-1 transcripts decreased following 1h of heat shock, but increased when L3s were incubated at 37°C for 1h. Activation of hookworm L3s induces a five-sixfold increase in Ac-hsb-1 expression that peaks at 12h, coincident with L3 feeding, but that subsequently decreases to two-threefold above control at 24h. Recombinant Ac-HSB-1 immunoprecipitates greater amounts of 70 and 40kDa proteins from extracts of activated L3s than from non-activated L3s. We propose that an increase in Ac-hsb-1 levels early in activation allows feeding to resume, but that a subsequent decrease in expression permits a HSR that protects non-developing L3s at host-like temperatures. Further investigations of the HSR will clarify the role of HSB-1 and HSF-1 in hookworm infection.


Subject(s)
Ancylostoma/growth & development , Ancylostoma/physiology , Heat-Shock Proteins/metabolism , Helminth Proteins/metabolism , Amino Acid Sequence , Ancylostoma/chemistry , Ancylostoma/genetics , Ancylostomiasis/metabolism , Ancylostomiasis/parasitology , Animals , Caenorhabditis elegans , Dogs , Heat-Shock Proteins/chemistry , Heat-Shock Proteins/genetics , Heat-Shock Response , Helminth Proteins/chemistry , Helminth Proteins/genetics , Humans , Larva/chemistry , Larva/genetics , Larva/growth & development , Larva/metabolism , Molecular Sequence Data , Protein Binding , Sequence Alignment
17.
Parasit Vectors ; 2(1): 21, 2009 Apr 24.
Article in English | MEDLINE | ID: mdl-19393088

ABSTRACT

BACKGROUND: Third-stage infective larvae (L3) of hookworms are in an obligatory state of developmental arrest that ends upon entering the definitive host, where they receive a signal that re-activates development. Recovery from the developmentally arrested dauer stage of Caenorhabditis elegans is analogous to the resumption of development during hookworm infection. Insulin-like signaling (ILS) mediates recovery from arrest in C. elegans and activation of hookworm dauer L3. In C. elegans, phosphorylation of the forkhead transcription factor DAF-16 in response to ILS creates binding cites for the 14-3-3 protein Ce-FTT-2, which translocates DAF-16 out of the nucleus, resulting in resumption of reproductive development. RESULTS: To determine if hookworm 14-3-3 proteins play a similar role in L3 activation, hookworm FTT-2 was identified and tested for its ability to interact with A. caninum DAF-16 in vitro. The Ac-FTT-2 amino acid sequence was 91% identical to the Ce-FTT-2, and was most closely related to FTT-2 from other nematodes. Ac-FTT-2 was expressed in HEK 293T cells, and was recognized by an antibody against human 14-3-3beta isoform. Reciprocal co-immunoprecipitations using anti-epitope tag antibodies indicated that Ac-FTT-2 interacts with Ac-DAF-16 when co-expressed in serum-stimulated HEK 293T cells. This interaction requires intact Akt consensus phosphorylation sites at serine107 and threonine312, but not serine381. Ac-FTT-2 was undetectable by Western blot in excretory/secretory products from serum-stimulated (activated) L3 or adult A. caninum. CONCLUSION: The results indicate that Ac-FTT-2 interacts with DAF-16 in a phosphorylation-site dependent manner, and suggests that Ac-FTT-2 mediates activation of L3 by binding Ac-DAF-16 during hookworm infection.

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