RESUMO
Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.
Assuntos
Regeneração , Medicina Regenerativa , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Medicina Regenerativa/métodos , Animais , Doenças Vasculares/terapia , Doenças Vasculares/fisiopatologia , Bioimpressão/métodos , Vasos Sanguíneos/fisiologia , Impressão TridimensionalRESUMO
PURPOSE OF REVIEW: To provide timely and relevant insights into the complex relationship between pulmonary vascular disease (PVD) and chronic lung disease (CLD), focusing on the causative and consequential dynamics between these conditions. RECENT FINDINGS: There are shared pathogenic mechanisms between pulmonary arterial hypertension (PAH) and group 3 pulmonary hypertension, including altered expression of mediators and growth factors implicated in both conditions. Factors such as hypoxia, hypoxemia, and hypercapnia also contribute to pulmonary vascular remodelling and endothelial dysfunction. However, the role of hypoxia as the sole driver of pulmonary hypertension in CLD is being reconsidered, particularly in chronic obstructive pulmonary disease (COPD), with evidence suggesting a potential role for cigarette smoke products in initiating pulmonary vascular impairment. On the other hand, interstitial lung disease (ILD) encompasses a group of heterogeneous lung disorders characterized by inflammation and fibrosis of the interstitium, leading to impaired gas exchange and progressive respiratory decline, which could also play a role as a cause of pulmonary hypertension. SUMMARY: Understanding the intricate interplay between the pulmonary vascular compartment and the parenchymal and airway compartments in respiratory disease is crucial for developing effective diagnostic and therapeutic strategies for patients with PVD and CLD, with implications for both clinical practice and research.
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Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/epidemiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Comorbidade , Doença Crônica , Hipóxia/fisiopatologia , Pneumopatias/fisiopatologia , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Remodelação Vascular/fisiologia , Doenças Vasculares/fisiopatologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia , Doenças Vasculares/complicaçõesRESUMO
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is the most prevalent sleep and respiratory disorder. This syndrome can induce severe cardiovascular and cerebrovascular complications, and intermittent hypoxia is a pivotal contributor to this damage. Vascular pathology is closely associated with the impairment of target organs, marking a focal point in current research. Vascular lesions are the fundamental pathophysiological basis of multiorgan ailments and indicate a shared pathogenic mechanism among common cardiovascular and cerebrovascular conditions, suggesting their importance as a public health concern. Increasing evidence shows a strong correlation between OSAHS and vascular lesions. Previous studies predominantly focused on the pathophysiological alterations in OSAHS itself, such as intermittent hypoxia and fragmented sleep, leading to vascular disruptions. This review aims to delve deeper into the vascular lesions affected by OSAHS by examining the microscopic pathophysiological mechanisms involved. Emphasis has been placed on examining how OSAHS induces vascular lesions through disruptions in the endothelial barrier, metabolic dysregulation, cellular phenotype alterations, neuroendocrine irregularities, programmed cell death, vascular inflammation, oxidative stress and epigenetic modifications. This review examines the epidemiology and associated risk factors for OSAHS and vascular diseases and subsequently describes the existing evidence on vascular lesions induced by OSAHS in the cardiovascular, cerebrovascular, retinal, renal and reproductive systems. A detailed account of the current research on the pathophysiological mechanisms mediating vascular lesions caused by OSAHS is provided, culminating in a discussion of research advancements in therapeutic modalities to mitigate OSAHS-related vascular lesions and the implications of these treatment strategies.
Assuntos
Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Fatores de Risco , Doenças Vasculares/fisiopatologia , Doenças Vasculares/complicações , Doenças Vasculares/epidemiologia , Doenças Cardiovasculares/epidemiologiaRESUMO
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed cause of acute coronary syndrome, particularly in younger women. Due to limited information about SCAD, case reports and case series can provide valuable insights into its features and management. This study aimed to comprehensively evaluate the features of SCAD patients who experienced psychophysical stress before the SCAD event. METHODS: We conducted an electronic search of PubMed, Scopus, and Web of Science from inception until January 7, 2023. We included case reports or series that described patients with SCAD who had experienced psychophysical stress before SCAD. Patients with pregnancy-associated SCAD were excluded from our analysis. RESULTS: In total, we included 93 case reports or series describing 105 patients with SCAD. The average patient age was 44.29 ± 13.05 years and a total of 44 (41.9%) of patients were male. Among the included SCAD patients the most prevalent comorbidities were fibromuscular dysplasia (FMD) and hypertension with the prevalence of 36.4 and 21.9%, respectively. Preceding physical stress was more frequently reported in men than in women; 38 out of 44 (86.4%) men reported physical stress, while 36 out of 61 (59.1%) females reported physical stress (p value = 0.009). On the other hand, the opposite was true for emotional stress (men: 6 (13.6%)), women: 29 (47.6%), p value < 0.001). Coronary angiography was the main diagnostic tool. The most frequently involved artery was the left anterior descending (LAD) (62.9%). In our study, recurrence of SCAD due to either the progression of a previous lesion or new SCAD in another coronary location occurred more frequently in those treated conservatively, however the observed difference was not statistically significant (p value = 0.138). CONCLUSION: While physical stress seems to precede SCAD in most cases, emotional stress is implicated in females more than males.
Assuntos
Anomalias dos Vasos Coronários , Estresse Psicológico , Doenças Vasculares , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relatos de Casos como Assunto , Comorbidade , Anomalias dos Vasos Coronários/epidemiologia , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais , Estresse Psicológico/epidemiologia , Estresse Psicológico/diagnóstico , Doenças Vasculares/congênito , Doenças Vasculares/epidemiologia , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/psicologia , Doenças Vasculares/fisiopatologia , Doenças Vasculares/diagnósticoRESUMO
Forced postures are common in the workplace. Work in the primary economic sector is characterised by a high degree of physical activity and movement; however, activities in the secondary and tertiary sectors commonly require workers to stand or sit. An expansion of the tertiary sector in recent decades has meant that people in industrialised and emerging economies primarily sit or stand at work. The aim of the systematic review was to identify occupational factors relating to the presence of chronic venous disease (CVD), to place these in the context of developments in the workplace, and to determine whether measures are in place to prevent CVD. We performed a systematic literature review to analyse studies assessing work-related risk factors for CVD. We searched for publications in the PubMed database, the clinic library of BG Hospital Bergmannstrost Halle, and the registry of the German Statutory Accident Insurance. Using occupation-specific keyword combinations, we identified 27,522 publications. The publications underwent an automatic and manual filtering process according to the PRISMA guidelines and 81 publications qualified for the review. Ultimately 25 studies were included in the systematic review. All of the subjects of the studies worked in the secondary and tertiary sectors. No studies looked at the relationship between venous disorders and primary sector occupations. Standing at work for more than four hours a day, repeated heavy lifting, and cumulative time working in a sitting or standing position are risk factors for the development of CVD. Sitting is less of a risk factor than standing or walking. Occupational history and the patient's activity profile are important diagnostic tools which can help confirm a diagnosis and justify treatment when findings are inconsistent. Compression therapy is the primary form of secondary and tertiary prevention. There continues to be a lack of primary preventive measures related to workplace design.
Assuntos
Doenças Profissionais , Saúde Ocupacional , Humanos , Fatores de Risco , Doenças Profissionais/epidemiologia , Doenças Profissionais/fisiopatologia , Doenças Profissionais/diagnóstico , Doenças Profissionais/prevenção & controle , Doenças Profissionais/etiologia , Postura , Doenças Vasculares/epidemiologia , Doenças Vasculares/fisiopatologia , Doenças Vasculares/diagnóstico , Medição de Risco , Masculino , Feminino , Descrição de Cargo , Exposição Ocupacional/efeitos adversos , Posição Ortostática , Doença CrônicaRESUMO
BACKGROUND: The etiology and significance of coronary artery tortuosity (TCA) among patients with spontaneous coronary artery dissection (SCAD) are unknown. The aim of this prospective imaging cohort study was to report echocardiographic findings and evaluate whether TCA correlates with cardiac anatomy and function among patients with SCAD. Comorbidities including fibromuscular dysplasia (FMD) and outcomes were also assessed. METHODS: TCA was determined on coronary angiography performed during the diagnosis of SCAD, and cardiac structure and function were evaluated using prospective comprehensive echocardiography. RESULTS: Among 116 patients with SCAD, the mean age at echocardiography was 50.8 ± 8.8 years, a median of 10.9 months after SCAD. Sixty-two patients (53.4%) had FMD, 41 (35.3%) had histories of hypertension, and 17 (14.8%) were hypertensive during echocardiography. Most patients (n = 78 [69%]) had normal left ventricular geometry with normal median ejection fraction (61%; interquartile range, 56% to 64%) and normal global longitudinal strain (-22.2%; interquartile range, -24.0% to -19.9%). Fifteen patients (13.4%) had diastolic dysfunction that was associated with hypertension at the time of echocardiography. Patients with TCA (n = 96 [82.8%]) were older (mean age, 52.1 ± 8.0 vs 44.7 ± 9.9 years; P < .001) with a higher prevalence of FMD (59.4% vs 25%, P = .007) but a similar prevalence of hypertension (35% vs 35%, P > .99) compared with patients without TCA. Across the age range (31.5 to 66.9 years), each decade of age was associated with an approximately 0.89-unit increase in coronary tortuosity score (P < .0001). Echocardiographic parameters were not significantly different between the two groups. Median follow-up duration was 4.4 years (95% CI, 3.8 to 5.2 years). The Kaplan-Meier 3-year SCAD recurrence rate was 9.4% (95% CI, 3.7% to 14.8%). There were no deaths. CONCLUSIONS: The majority of patients with SCAD had normal or near normal echocardiographic results, including global longitudinal strain, with no differences according to TCA. However, patients with SCAD with TCA were older, with a higher prevalence of FMD.
Assuntos
Anomalias dos Vasos Coronários , Vasos Coronários , Ecocardiografia , Displasia Fibromuscular , Doenças Vasculares , Doenças Vasculares/congênito , Humanos , Feminino , Masculino , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/epidemiologia , Displasia Fibromuscular/fisiopatologia , Pessoa de Meia-Idade , Anomalias dos Vasos Coronários/epidemiologia , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico , Anomalias dos Vasos Coronários/fisiopatologia , Ecocardiografia/métodos , Estudos Prospectivos , Doenças Vasculares/epidemiologia , Doenças Vasculares/fisiopatologia , Doenças Vasculares/diagnóstico , Doenças Vasculares/complicações , Vasos Coronários/diagnóstico por imagem , Angiografia Coronária/métodos , Adulto , Deformação Longitudinal GlobalRESUMO
The understanding of the function of perivascular adipose tissue (PVAT) in vascular aging has significantly changed due to the increasing amount of information regarding its biology. Adipose tissue surrounding blood vessels is increasingly recognized as a key regulator of vascular disorders. It has significant endocrine and paracrine effects on the vasculature and is mediated by the production of a variety of bioactive chemicals. It also participates in a number of pathological regulatory processes, including oxidative stress, immunological inflammation, lipid metabolism, vasoconstriction, and dilation. Mechanisms of homeostasis and interactions between cells at the local level tightly regulate the function and secretory repertoire of PVAT, which can become dysregulated during vascular aging. The PVAT secretion group changes from being reducing inflammation and lowering cholesterol to increasing inflammation and increasing cholesterol in response to systemic or local inflammation and insulin resistance. In addition, the interaction between the PVAT and the vasculature is reciprocal, and the biological processes of PVAT are directly influenced by the pertinent indicators of vascular aging. The architectural and biological traits of PVAT, the molecular mechanism of crosstalk between PVAT and vascular aging, and the clinical correlation of vascular age-related disorders are all summarized in this review. In addition, this paper aims to elucidate and evaluate the potential benefits of therapeutically targeting PVAT in the context of mitigating vascular aging. Furthermore, it will discuss the latest advancements in technology used for targeting PVAT.
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Tecido Adiposo , Envelhecimento , Vasos Sanguíneos , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Animais , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/metabolismo , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologiaAssuntos
Anomalias dos Vasos Coronários , Intervenção Coronária Percutânea , Doenças Vasculares , Doenças Vasculares/congênito , Humanos , Intervenção Coronária Percutânea/métodos , Anomalias dos Vasos Coronários/cirurgia , Anomalias dos Vasos Coronários/fisiopatologia , Anomalias dos Vasos Coronários/diagnóstico , Masculino , Doenças Vasculares/fisiopatologia , Doenças Vasculares/cirurgia , Feminino , Pessoa de Meia-Idade , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Vasos Coronários/cirurgia , Circulação Coronária/fisiologia , Resultado do Tratamento , AdultoRESUMO
BACKGROUND: Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification. MATERIALS AND METHODS: On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as "Heart failure with preserved ejection fraction," "HFpEF," "microvascular dysfunction," and "MVD." The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF. RESULTS: Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%-76.2%), with a substantial degree of heterogeneity (I2 = 98%, p for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them. CONCLUSIONS: This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.
Assuntos
Vasos Coronários , Insuficiência Cardíaca , Microvasos , Doenças Vasculares , Humanos , Insuficiência Cardíaca/fisiopatologia , Prognóstico , Volume Sistólico/fisiologia , Doenças Vasculares/fisiopatologia , Microvasos/fisiopatologia , Vasos Coronários/fisiopatologia , Circulação Coronária/fisiologiaRESUMO
BACKGROUND: Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population. METHODS: Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx. RESULTS: The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p < .0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p < .001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p < .0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF. CONCLUSIONS: Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Doenças Vasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Hemodinâmica , Circulação Pulmonar/fisiologia , Estudos Retrospectivos , Doenças Vasculares/complicações , Doenças Vasculares/mortalidade , Doenças Vasculares/fisiopatologia , Resistência Vascular/fisiologiaRESUMO
Laser speckle contrast imaging (LSCI) is a powerful visualization tool for quantifying blood flow in tissues, providing simplicity of configuration, ease of use, and intuitive results. With recent advancements, smartphone and camera technologies are suitable for the development of smartphone-based LSCI applications for point-of-care (POC) diagnosis. A smartphone-based portable LSCI endoscope system was validated for POC diagnosis of vascular disorders. The endoscope consisted of compact LED and laser illumination, imaging optics, and a flexible fiberscope assembled in a 3D-printed hand-held cartridge for access to body cavities and organs. A smartphone's rear camera was mounted thereto, enabling endoscopy, LSCI image acquisition, and processing. Blood flow imaging was calibrated in a perfused tissue phantom consisting of a microparticle solution pumped at known rates through tissue-mimicking gel and validated in a live rat model of BBN-induced bladder cancer. Raw LSCI images successfully visualized phantom flow: speckle flow index showed linearity with the pump flow rate. In the rat model, healthy and cancerous bladders were distinguishable in structure and vasculature. The smartphone-based low-cost portable mobile endoscope for monitoring blood flow and perfusion shows promise for preclinical applications and may be suitable for primary diagnosis at home or as a cost-effective POC testing assay.
Assuntos
Imagem de Contraste de Manchas a Laser , Sistemas Automatizados de Assistência Junto ao Leito , Fluxo Sanguíneo Regional/fisiologia , Smartphone , Doenças Vasculares/diagnóstico , Animais , Endoscópios , Imagens de Fantasmas , Ratos , Neoplasias da Bexiga Urinária/irrigação sanguínea , Doenças Vasculares/fisiopatologiaRESUMO
It is well known that cardiovascular disease manifests differently in women and men. The underlying causes of these differences during the aging lifespan are less well understood. Sex differences in cardiac and vascular phenotypes are seen in childhood and tend to track along distinct trajectories related to dimorphism in genetic factors as well as response to risk exposures and hormonal changes during the life course. These differences underlie sex-specific variation in cardiovascular events later in life, including myocardial infarction, heart failure, ischemic stroke, and peripheral vascular disease. With respect to cardiac phenotypes, females have intrinsically smaller body size-adjusted cardiac volumes and they tend to experience greater age-related wall thickening and myocardial stiffening with aging. With respect to vascular phenotypes, sexual dimorphism in both physiology and pathophysiology are also seen, including overt differences in blood pressure trajectories. The majority of sex differences in myocardial and vascular alterations that manifest with aging seem to follow relatively consistent trajectories from the very early to the very later stages of life. This review aims to synthesize recent cardiovascular aging-related research to highlight clinically relevant studies in diverse female and male populations that can inform approaches to improving the diagnosis, management, and prognosis of cardiovascular disease risks in the aging population at large.
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Envelhecimento/patologia , Cardiomiopatias/fisiopatologia , Vasos Coronários/patologia , Caracteres Sexuais , Doenças Vasculares/fisiopatologia , Envelhecimento/fisiologia , Cardiomiopatias/diagnóstico , Vasos Coronários/fisiologia , Feminino , Humanos , Masculino , Miocárdio/patologia , Doenças Vasculares/diagnósticoRESUMO
Sarcopenia characterized by reduced skeletal muscle mass and decreased muscle strength is increasing in prevalence globally. The pathophysiology of sarcopenia is related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction of food intake, advanced age, low body mass index, and low physical activity. Recently, sarcopenia has been reported to be associated with cognitive decline, and the common risk factors between sarcopenia and memory loss were observed in cohort studies. Many researchers suggested that the prevalence of sarcopenia is associated with vascular disorder, such as atherosclerosis and alteration of intracellular mechanisms caused by changes in myokine secretion. We herein review the emerging evidence on the strong link between cognitive impairment and sarcopenia, focusing on myokine secretion and vascular dysfunction, and provide an understanding of the relevant mechanisms and crucial determinants in cognitive decline caused by sarcopenia.
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Disfunção Cognitiva/fisiopatologia , Citocinas/metabolismo , Músculo Esquelético/fisiologia , Sarcopenia/fisiopatologia , Doenças Vasculares/fisiopatologia , Disfunção Cognitiva/epidemiologia , Humanos , Força Muscular/fisiologia , Fatores de Risco , Sarcopenia/epidemiologia , Doenças Vasculares/epidemiologiaRESUMO
Various clinically applicable scores and indices are available to help identify the state of a microcirculatory disorder in a patient. Several of these methods, however, leave room for interpretation and only provide clues for diagnosis. Thus, a measurement method that allows a reliable detection of impending or manifest circulatory malfunctions would be of great value. In this context, the optical and non-invasive method of shifted position-diffuse reflectance imaging (SP-DRI) was developed. It allows to determine the capillary diameter and thus to assess the state of the microcirculation. The aim of the present study is to investigate how the quantification of capillary diameters by SP-DRI behaves in different individuals, i.e. for a wide range of optical properties. For this, within Monte-Carlo simulations all optical properties (seven skin layers, hemoglobin) were randomly varied following a Gaussian distribution. An important finding from the present investigation is that SP-DRI works when the optical properties are chosen randomly. Furthermore, it is shown that appropriate data analysis allows calibration-free absolute quantification of the capillary diameter across individuals using SP-DRI. This underpins the potential of SP-DRI to serve as an early alert system for the onset of microcirculatory associated diseases.
Assuntos
Capilares/diagnóstico por imagem , Microcirculação , Imagem Óptica , Pele/irrigação sanguínea , Doenças Vasculares/diagnóstico por imagem , Algoritmos , Capilares/fisiopatologia , Simulação por Computador , Humanos , Modelos Cardiovasculares , Método de Monte Carlo , Oxiemoglobinas/metabolismo , Doenças Vasculares/sangue , Doenças Vasculares/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVES: Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a randomized, placebo-controlled, double-blind trial, 68 children/young adults 6-25 years of age with ADPKD and eGFR>80 ml/min per 1.73 m2 were randomized to either curcumin supplementation (25 mg/kg body weight per day) or placebo administered in powder form for 12 months. The coprimary outcomes were brachial artery flow-mediated dilation and aortic pulse-wave velocity. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume) by magnetic resonance imaging. In a subgroup of participants ≥18 years, vascular oxidative stress was measured as the change in brachial artery flow-mediated dilation following an acute infusion of ascorbic acid. RESULTS: Enrolled participants were 18±5 (mean ± SD) years, 54% were girls, baseline brachial artery flow-mediated dilation was 9.3±4.1% change, and baseline aortic pulse-wave velocity was 512±94 cm/s. Fifty-seven participants completed the trial. Neither coprimary end point changed with curcumin (estimated change [95% confidence interval] for brachial artery flow-mediated dilation [percentage change]: curcumin: 1.14; 95% confidence interval, -0.84 to 3.13; placebo: 0.33; 95% confidence interval, -1.34 to 2.00; estimated difference for change: 0.81; 95% confidence interval, -1.21 to 2.84; P=0.48; aortic pulse-wave velocity [centimeters per second]: curcumin: 0.6; 95% confidence interval, -25.7 to 26.9; placebo: 6.5; 95% confidence interval, -20.4 to 33.5; estimated difference for change: -5.9; 95% confidence interval, -35.8 to 24.0; P=0.67; intent to treat). There was no curcumin-specific reduction in vascular oxidative stress or changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared with placebo. CONCLUSIONS: Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD, NCT02494141. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN08950621.mp3.
Assuntos
Curcumina/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Rim Policístico Autossômico Dominante/fisiopatologia , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/fisiopatologia , Rigidez Vascular/efeitos dos fármacos , Adolescente , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The microcirculation includes all blood and lymph vessels with a diameter <â100âµm. Microcirculatory dysfunction is common in critically ill patients and is closely associated with both the severity of (multi-)organ dysfunction and mortality. The nature and extent of microcirculatory dysfunction differ depending on the underlying disease and are most pronounced in patients with systemic inflammation (e.âg. sepsis), specific infections (e.âg. malaria, dengue) or thrombocytopenia-associated multiple organ failure. This manuscript provides an overview of the pathophysiology, monitoring and therapy of microcirculatory dysfunction in the critically ill patient.