RESUMO
PURPOSE OF REVIEW: Lipids and lipoproteins have long been known to contribute to atherosclerosis and cardiovascular calcification. One theme of recent work is the study of lipoprotein (a) [Lp(a)], a lipoprotein particle similar to LDL-cholesterol that carries a long apoprotein tail and most of the circulating oxidized phospholipids. RECENT FINDINGS: In-vitro studies show that Lp(a) stimulates osteoblastic differentiation and mineralization of vascular smooth muscle cells, while the association of Lp(a) with coronary artery calcification continues to have varying results, possibly because of the widely varying threshold levels of Lp(a) chosen for association analyses. Another emerging area in the field of cardiovascular calcification is pathological endothelial-to-mesenchymal transition (EndMT), the process whereby endothelial cell transition into multipotent mesenchymal cells, some of which differentiate into osteochondrogenic cells and mineralize. The effects of lipids and lipoproteins on EndMT suggest that they modulate cardiovascular calcification through multiple mechanisms. There are also emerging trends in imaging of calcific vasculopathy, including: intravascular optical coherence tomography for quantifying plaque characteristics, PET with a radiolabeled NaF tracer, with either CT or MRI to detect coronary plaque vulnerability. SUMMARY: Recent work in this field includes studies of Lp(a), EndMT, and new imaging techniques.
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Aterosclerose , Calcinose , Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Lipoproteína(a) , Lipoproteínas LDLRESUMO
STUDY OBJECTIVE: To evaluate the impact of the new donor heart allocation system implemented in the United States in October 2018 on development of early cardiac allograft vasculopathy (CAV). DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) heart transplant recipients registered in the United Network for Organ Sharing database between October 18, 2015 and October 17, 2018 (old system) and October 18, 2018 and May 31, 2020 (new system). MAIN OUTCOME MEASURE: Incidence of angiographic CAV at 1 year (accelerated CAV) in the overall transplant population and among the highest acuity subgroup-Status 1A (old) and Status 1 or 2 (new). We included recipient and donor demographic, cardiovascular, and transplant factors in multivariable logistic regression models to identify predictors of accelerated CAV. RESULTS: Of 10,375 transplant recipients, 6,660 (64%) and 3,715 (36%) were listed in the old and new allocation cohorts, respectively. The incidence of accelerated CAV was 521 (8%) in the old period compared with 272 (7%) in the new period (P = .36). Similar incidence rates were observed in the highest acuity subgroup-363 (8%) compared with 143 (7%), respectively (P = .13). In adjusted analyses of the high-acuity cohort, the new allocation system was not associated with a higher likelihood of accelerated CAV (odds ratio = 0.87, 95% confidence interval: 0.70-1.08, P = .20). CONCLUSIONS: The new donor heart allocation system is not associated with development of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.
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Transplante de Coração , Doadores de Tecidos , Adulto , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Transplantados , IncidênciaRESUMO
PURPOSE OF REVIEW: Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in atherosclerosis are also established, and lipid-modifying therapies have shown capacity for plaque regression. However, the association of lipid-modifying therapies with calcification is more complex, and currently no medical therapies have been found to reverse or attenuate calcification in patients. In this review, we summarize recent developments in our understanding of the interplay between lipids and cardiovascular calcification, as well as new imaging modalities for assessing calcified atherosclerotic plaque vulnerability. RECENT FINDINGS: Recent clinical studies have highlighted the associations of lipoprotein subtypes, such as low-density and high-density lipoprotein particles, as well as lipoprotein (a) [Lp(a)], with coronary calcification and calcific aortic valve disease. Further, evidence continues to emerge for the utility of fused 18F-sodium fluoride positron-emission tomographic and computed tomographic (18F-NaF PET/CT) imaging in characterizing the microarchitecture and vulnerability of atherosclerotic plaque, in both humans and animal models. SUMMARY: The relationship between lipids and cardiovascular calcification is complex, and new imaging techniques, such as 18F-NaF PET/CT imaging, may allow for better identification of disease-modifying therapies and prediction of calcified plaque progression and stability to help guide clinical management.
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Placa Aterosclerótica , Animais , Humanos , Lipídeos , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Fluoreto de SódioRESUMO
BACKGROUND: Despite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology. METHODS: To test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF µPET/µCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry. RESULTS: Results showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold. CONCLUSION: These findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.
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Calcificação Fisiológica/fisiologia , Hiperlipidemias/complicações , Condicionamento Físico Animal/normas , Placa Aterosclerótica/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Fluordesoxiglucose F18/administração & dosagem , Fluordesoxiglucose F18/uso terapêutico , Hiperlipidemias/diagnóstico por imagem , Camundongos , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/estatística & dados numéricos , Placa Aterosclerótica/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly infecting people worldwide, resulting in the infectious disease coronavirus disease 19 (COVID-19) that has been declared a pandemic. Much remains unknown about COVID-19, including its effects on solid organ transplant (SOT) recipients. Given their immunosuppressed state, SOT recipients are presumed to be at high risk of complications with viral infections such as SARS-CoV-2. Limited case reports in single SOT recipients, however, have not suggested a particularly severe course in this population. In this report, we present a dual-organ (heart/kidney) transplant recipient who was found to have COVID-19 and, despite the presence of a number of risk factors for poor outcomes, had a relatively mild clinical course.
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Cardiomiopatia Dilatada/complicações , Infecções por Coronavirus/diagnóstico , Transplante de Coração , Falência Renal Crônica/complicações , Transplante de Rim , Pneumonia Viral/diagnóstico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Adulto , Alanina/administração & dosagem , Alanina/análogos & derivados , Betacoronavirus , COVID-19 , Cardiomiopatia Dilatada/cirurgia , Infecções por Coronavirus/complicações , Humanos , Hidroxicloroquina/administração & dosagem , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Falência Renal Crônica/cirurgia , Masculino , Pandemias , Pneumonia Viral/complicações , Radiografia Torácica , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , SARS-CoV-2 , Resultado do TratamentoRESUMO
Coronavirus disease 2019 (COVID-19) is a global pandemic. In the USA, the burden of mortality and morbidity has fallen on minority populations. The understanding of the impact of this pandemic has been limited in Asian-Americans and Pacific Islanders (AAPIs), though disaggregated data suggest disproportionately high mortality rates. AAPIs are at high risk for COVID-19 transmission, in part due to their over-representation in the essential workforce, but also due to cultural factors, such as intergenerational residency, and other social determinants of health, including poverty and lack of health insurance. Some AAPI subgroups also report a high comorbidity burden, which may increase their susceptibility to more severe COVID-19 infection. Furthermore, AAPIs have encountered rising xenophobia and racism across the country, and we fear such discrimination only serves to exacerbate these rapidly emerging disparities in this community. We recommend interventions including disaggregation of mortality and morbidity data, investment in community-based healthcare, advocacy against discrimination and the use of non-inflammatory language, and a continued emphasis on underlying comorbidities, to ensure the protection of vulnerable communities and the navigation of this current crisis.
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COVID-19/etnologia , Disparidades em Assistência à Saúde/etnologia , Asiático , COVID-19/mortalidade , Comorbidade , Estudos Epidemiológicos , Pessoal de Saúde/estatística & dados numéricos , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Pandemias , Racismo , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations.
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Doenças Cardiovasculares/etiologia , Vitamina D/administração & dosagem , Vitamina D/metabolismo , Vitaminas/administração & dosagem , Vitaminas/metabolismo , Fatores Etários , Aterosclerose/etiologia , Cálcio da Dieta/administração & dosagem , Cálcio da Dieta/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Colecalciferol/biossíntese , Colecalciferol/metabolismo , Fatores de Confusão Epidemiológicos , Suplementos Nutricionais/efeitos adversos , Esquema de Medicação , Alimentos , Guias como Assunto , Humanos , Hidroxilação , Estudos Observacionais como Assunto , Medicina de Precisão , Receptores de LDL/metabolismo , Luz Solar , Calcificação Vascular/etiologia , Vitamina D/efeitos adversos , Vitamina D/biossíntese , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Vitaminas/efeitos adversosRESUMO
The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.
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COVID-19/prevenção & controle , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Complicações Pós-Operatórias/prevenção & controle , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/etiologia , Teste para COVID-19 , Feminino , Humanos , Controle de Infecções/métodos , Los Angeles/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: To describe the epidemiology, pathophysiology, management, and prognosis of patients with heart failure with mid-range ejection fraction (HFmrEF). RECENT FINDINGS: In 2013, The American Heart Association (AHA)/American College of Cardiology (ACC) assigned an ejection fraction (EF) range to heart failure with reduced ejection fraction (HFrEF, EF ≤ 40%) and heart failure with preserved ejection fraction (HFpEF, EF ≥50%). This classification created a "gray zone" of patients with EFs between 41% and 49% that ultimately came to be known as heart failure with borderline or mid-range ejection fraction. HFmrEF patients represent a group with heterogeneous clinical characteristics that at times resembles HFrEF, at others HFpEF, and at others still a unique phenotype altogether. No randomized controlled trials exist in those with HFmrEF, though HFrEF and HFpEF studies that include overlap suggest some potential benefit of beta blockers, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. Mortality rates among the HFmrEF population are significant, and are similar to those in patients with HFrEF and HFpEF. HFmrEF is a complex disorder that remains poorly understood. Future research is needed to better elucidate the pathophysiology, management, and prognosis of this condition.
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Gerenciamento Clínico , Insuficiência Cardíaca/fisiopatologia , Sistema de Registros , Volume Sistólico/fisiologia , Saúde Global , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Morbidade/tendências , Prognóstico , Fatores de RiscoRESUMO
Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit the onset of aortic calcification. Whether teriparatide affects the progression of preexisting aortic calcification, widespread among this patient population, is unknown. Female apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic calcification, treated for 4.5 wk with daily injections of control vehicle (PBS), 40 µg/kg teriparatide (PTH40), or 400 µg/kg teriparatide (PTH400), and assayed for aortic calcification by microcomputed tomography (microCT) before and after treatment. In a followup cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400 and assayed for aortic calcification by serial microCT and micropositron emission tomography. In both cohorts, aortic calcification detected by microCT progressed similarly in all groups. Mean aortic 18F-NaF incorporation, detected by serial micropositron emission tomography, increased in the PBS-treated group (+14 ± 5%). In contrast, 18F-NaF incorporation decreased in the PTH400-treated group (-33 ± 20%, P = 0.03). Quantitative histochemical analysis by Alizarin red staining revealed a lower mineral surface area index in the PTH400-treated group compared with the PBS-treated group ( P = 0.04). Furthermore, Masson trichrome staining showed a significant increase in collagen deposition in the left ventricular myocardium of mice that received PTH400 [2.1 ± 0.6% vs. control mice (0.5 ± 0.1%), P = 0.02]. In summary, although teriparatide may not affect the calcium mineral content of aortic calcification, it reduces 18F-NaF uptake in calcified lesions, suggesting the possibility that it may reduce mineral surface area with potential impact on plaque stability. NEW & NOTEWORTHY Parathyroid hormone regulates bone mineralization and may also affect vascular calcification, which is an important issue, given that its active fragment, teriparatide, is widely used for the treatment of osteoporosis. To determine whether teriparatide alters vascular calcification, we imaged aortic calcification in mice treated with teriparatide and control mice. Although teriparatide did not affect the calcium content of cardiovascular deposits, it reduced their fluoride tracer uptake.
Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Conservadores da Densidade Óssea/farmacologia , Hiperlipidemias/complicações , Teriparatida/farmacologia , Calcificação Vascular/tratamento farmacológico , Fatores Etários , Envelhecimento , Animais , Aorta/diagnóstico por imagem , Aorta/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Aortografia/métodos , Aterosclerose/diagnóstico por imagem , Aterosclerose/etiologia , Aterosclerose/patologia , Conservadores da Densidade Óssea/toxicidade , Angiografia por Tomografia Computadorizada , Modelos Animais de Doenças , Feminino , Fibrose , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Camundongos Knockout para ApoE , Placa Aterosclerótica , Tomografia por Emissão de Pósitrons , Teriparatida/toxicidade , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologia , Calcificação Vascular/patologia , Microtomografia por Raio-XRESUMO
PURPOSE OF REVIEW: Real-time 3-dimensional (3-D) imaging of cardiovascular injury and regeneration remains challenging. We introduced a multi-scale imaging strategy that uses light-sheet illumination to enable applications of cardiovascular injury and repair in models ranging from zebrafish to rodent hearts. RECENT FINDINGS: Light-sheet imaging enables rapid data acquisition with high spatiotemporal resolution and with minimal photo-bleaching or photo-toxicity. We demonstrated the capacity of this novel light-sheet approach for scanning a region of interest with specific fluorescence contrast, thereby providing axial and temporal resolution at the cellular level without stitching image columns or pivoting illumination beams during one-time imaging. This cutting-edge imaging technique allows for elucidating the differentiation of stem cells in cardiac regeneration, providing an entry point to discover novel micro-circulation phenomenon with clinical significance for injury and repair. These findings demonstrate the multi-scale applications of this novel light-sheet imaging strategy to advance research in cardiovascular development and regeneration.
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Doenças Cardiovasculares/diagnóstico por imagem , Traumatismos Cardíacos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Miocárdio/patologia , Regeneração/fisiologia , Peixe-Zebra/embriologia , Animais , Doenças Cardiovasculares/patologia , Traumatismos Cardíacos/patologia , Microscopia de Fluorescência , Modelos Animais , Modelos Cardiovasculares , RoedoresRESUMO
In calcific aortic valve disease, the valve cusps undergo retraction, stiffening, and nodular calcification. The inflammatory cytokine, tumor necrosis factor (TNF)-α, contributes to valve disease progression; however, the mechanisms of its actions on cusp retraction and stiffening are unclear. We investigated effects of TNF-α on murine aortic valvular interstitial cells (VICs) within three-dimensional, free-floating, compliant, collagen hydrogels, simulating their natural substrate and biomechanics. TNF-α increased retraction (percentage of diameter), stiffness, and formation of macroscopic, nodular structures with calcification in the VIC-laden hydrogels. The effects of TNF-α were attenuated by blebbistatin inhibition of myosin II-mediated cytoskeletal contraction. Inhibition of actin polymerization with cytochalasin-D, but not inhibition of Rho kinase with Y27632, blocked TNF-α-induced retraction in three-dimensional VIC hydrogels, suggesting that actin stress fibers mediate TNF-α-induced effects. In the hydrogels, inhibitors of NF-κB blocked TNF-α-induced retraction, whereas simultaneous inhibition of c-Jun N-terminal kinase was required to block TNF-α-induced stiffness. TNF-α also significantly increased collagen deposition, as visualized by Masson's trichrome staining, and up-regulated mRNA expression of discoidin domain receptor tyrosine kinase 2, fibronectin, and α-smooth muscle actin. In human aortic valves, calcified cusps were stiffer and had more collagen deposition than noncalcified cusps. These findings suggest that inflammation, through stimulation of cytoskeletal contractile activity, may be responsible for valvular cusp retraction, stiffening, and formation of calcified nodules.
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Estenose da Valva Aórtica/patologia , Valva Aórtica/patologia , Calcinose/patologia , Citoesqueleto/patologia , Inflamação/patologia , Animais , Western Blotting , Técnicas de Cultura de Células , Células Cultivadas , Modelos Animais de Doenças , Imunofluorescência , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaAssuntos
Cardiologistas/educação , Infecções por Coronavirus/patologia , Liderança , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/epidemiologia , Tomada de Decisões , Atenção à Saúde , Educação Médica Continuada , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pesquisa , SARS-CoV-2RESUMO
RATIONALE: Left-right (LR) asymmetry is ubiquitous in animal development. Cytoskeletal chirality was recently reported to specify LR asymmetry in embryogenesis, suggesting that LR asymmetry in tissue morphogenesis is coordinated by single- or multi-cell organizers. Thus, to organize LR asymmetry at multiscale levels of morphogenesis, cells with chirality must also be present in adequate numbers. However, observation of LR asymmetry is rarely reported in cultured cells. OBJECTIVES: Using cultured vascular mesenchymal cells, we tested whether LR asymmetry occurs at the single cell level and in self-organized multicellular structures. METHODS AND RESULTS: Using micropatterning, immunofluorescence revealed that adult vascular cells polarized rightward and accumulated stress fibers at an unbiased mechanical interface between adhesive and nonadhesive substrates. Green fluorescent protein transfection revealed that the cells each turned rightward at the interface, aligning into a coherent orientation at 20° relative to the interface axis at confluence. During the subsequent aggregation stage, time-lapse videomicroscopy showed that cells migrated along the same 20° angle into neighboring aggregates, resulting in a macroscale structure with LR asymmetry as parallel, diagonal stripes evenly spaced throughout the culture. Removal of substrate interface by shadow mask-plating, or inhibition of Rho kinase or nonmuscle myosin attenuated stress fiber accumulation and abrogated LR asymmetry of both single-cell polarity and multicellular coherence, suggesting that the interface triggers asymmetry via cytoskeletal mechanics. Examination of other cell types suggests that LR asymmetry is cell-type specific. CONCLUSIONS: Our results show that adult stem cells retain inherent LR asymmetry that elicits de novo macroscale tissue morphogenesis, indicating that mechanical induction is required for cellular LR specification.
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Células-Tronco Adultas/fisiologia , Vasos Sanguíneos/embriologia , Polaridade Celular , Citoesqueleto/fisiologia , Mesoderma/fisiologia , Animais , Vasos Sanguíneos/citologia , Adesão Celular , Técnicas de Cultura de Células , Movimento Celular , Simulação por Computador , Vidro , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Mesoderma/citologia , Camundongos , Microscopia de Fluorescência , Microscopia de Vídeo , Modelos Biológicos , Morfogênese , Células NIH 3T3 , Análise Numérica Assistida por Computador , Fibras de Estresse/fisiologia , Propriedades de Superfície , Fatores de Tempo , Imagem com Lapso de Tempo , TransfecçãoRESUMO
BACKGROUND: Serum fibroblast growth factor-23 (FGF-23) is associated with cardiovascular disease (CVD), yet the mechanisms remain uncertain. Our objective was to determine whether higher FGF-23 concentrations are associated with arterial stiffness. METHODS: In this cross-sectional study, serum FGF-23 concentrations were measured in 5977 participants without known CVD in the Multi-Ethnic Study of Atherosclerosis. The primary outcomes of interest were large (LAE) and small artery elasticity (SAE), pulse pressure and ankle-brachial index (ABI) > 1.30. LAE and SAE were measured by pulse contour analysis of the radial artery. Pulse pressure was measured with an automated sphygmomanometer using the average of two resting blood pressure measurements. ABI was calculated as the ratio of the ankle and brachial systolic blood pressures. RESULTS: Serum FGF-23 concentrations were not significantly associated with LAE [relative difference (RD) per doubling: 0%; 95% confidence interval (CI): -2-1%], SAE (RD per doubling: 0%; 95% CI: -3-2%), pulse pressure (ß per doubling: 0.44; 95% CI: -0.31-1.19), or a high ABI (odds ratio per doubling: 1.14; 95% CI: 0.84-1.55). Findings were similar irrespective of chronic kidney disease status. CONCLUSIONS: Higher serum FGF-23 concentrations are not associated with arterial stiffness, as measured by pulse pressure, LAE, SAE or high ABI, in a community-based population without CVD.
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Aterosclerose/fisiopatologia , Etnicidade , Fatores de Crescimento de Fibroblastos/sangue , Vigilância da População , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Aterosclerose/sangue , Aterosclerose/etnologia , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Colorimetria , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Collagens have dual functions in the extracellular matrix (ECM), acting as both structural components and signaling molecules in matricellular communication. Although collagen molecules share a common triple helix motif, the supramolecular organization helps classify them into nearly 30 different types of collagens. Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen that is expressed throughout the vasculature. Collagen VIII expression is aberrant in cardiovascular, lung, and renal disease, as well as in several different types of cancer. It plays active roles in angiogenesis, vessel injury repair, maintenance of arterial compliance, atherosclerotic plaque formation and stability modulation, fibrosis, and ECM remodeling. This review presents an overview of the characteristics of collagen VIII in vascular-related disorders, from clinical significance to laboratory studies, with a major focus on highlighting the signaling properties of collagen VIII in the vascular ECM. The expression patterns of collagen VIII in human diseases and experimental animal models highlight the protein's important yet underexplored functions. A deeper understanding of its mechanisms and downstream signaling pathways may pave the way for translational and tissue engineering applications of collagen VIII.
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BACKGROUND: Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multiorgan transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multiorgan heart transplants in the contemporary era. METHODS: We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary end-point was the development of angiographic CAV within 5 years of follow-up. RESULTS: Among 20,591 patients included in the analysis, 1,279 (6%) underwent multiorgan heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ), and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years, and 74% were male. There were no significant between-group differences in cold ischemic time. The incidence of acute rejection during the first year after transplant was significantly lower in the multiorgan group (18% vs 33%, p < 0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multiorgan group (p < 0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multiorgan heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio = 0.76, 95% confidence interval: 0.66-0.88, p < 0.01). CONCLUSIONS: Simultaneous multiorgan heart transplantation is associated with a significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.
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Importance: Previous studies of professional basketball athletes have characterized manifestations of athletic remodeling by echocardiography and electrocardiography (ECG) in males and echocardiography in females. There is a paucity of female, basketball-specific ECG data. Objective: To generate reference range ECG data for female professional basketball athletes. Design, Setting, and Participants: This is a cross-sectional study of ECGs performed on female professional basketball athletes. The Women's National Basketball Association mandates annual preseason ECGs and echocardiograms for each athlete and has partnered with Columbia University Irving Medical Center to annually review these studies. Data for this study were collected during preseason ECG and echocardiography cardiac screening between April and May 2022. Data analysis was performed between February and July 2023. Exposure: Athlete ECGs and echocardiograms were sent to Columbia University Irving Medical Center for core lab analysis. Main Outcomes and Measures: Quantitative ECG variables were measured. ECG data were qualitatively analyzed for training-related and abnormal findings using the International Recommendations for Electrocardiographic Interpretation in Athletes. Findings from ECGs were compared with corresponding echocardiographic data. Results: There were a total of 173 athletes (mean [SD] age 26.5 [4.1] years; mean [SD] height, 183.4 [9.1] cm; mean [SD] body surface area, 2.0 [0.2] m2), including 129 Black athletes (74.5%) and 40 White athletes (23.1%). By international criteria, 136 athletes (78.6%) had training-related ECG changes and 8 athletes (4.6%) had abnormal ECG findings. Among athletes with at least 1 training-related ECG finding, left ventricular structural adaptations associated with athletic remodeling were present in 64 athletes (47.1%). Increased relative wall thickness, reflecting concentric left ventricular geometry, was more prevalent in athletes with the repolarization variant demonstrating convex ST elevation combined with T-wave inversions in leads V1 to V4 (6 of 12 athletes [50.0%]) than in athletes with early repolarization (5 of 42 athletes [11.9%]) (odds ratio, 7.40; 95% CI, 1.71-32.09; P = .01). Abnormal ECG findings included T-wave inversions (3 athletes [1.7%]), Q waves (2 athletes [1.2%]), prolonged QTc interval (2 athletes [1.2%]), and frequent premature ventricular contractions (1 athlete [0.6%]). Conclusions and Relevance: This cross-sectional study provides reference ECG data for elite female basketball athletes. International criteria-defined training-related findings were common, whereas abnormal ECG findings were rare in this athlete group. These reference data may assist basketball programs and health care professionals using ECGs in screening for female athletes and may be used as a stimulus for future female-specific ECG inquiries.