29 research outputs found
The Role of Vascular Smooth Muscle Cells in the Physiology and Pathophysiology of Blood Vessels
Vascular smooth muscle cells (VSMCs) play important roles not only in the physiological functions of the blood vessels, such as vasoconstriction, vasodilatation and extracellular matrix production, but also in the pathogenesis of vascular diseases, particularly atherosclerosis and hypertension. VSMCs are mostly of mesodermal origin, although some are of neuroectodermal origin, for example, VSMCs present in the aorta and in blood vessels arising from the aortic arch. VSMCs of neuroectodermal origin are implicated in defects of cardiovascular morphogenesis, such as bicuspid aortic valve, coarctation of the aorta, patent ductus arteriosus and tetralogy of Fallot. The origin, location in the vascular tree, gender, species, strain and age influence the phenotype of VSMCs and their propensity to migration and growth. In a healthy adult organism, VSMCs have a quiescent and differentiated contractile phenotype characterized by early markers (e.g., SM α-actin, SM22-α), intermediate markers (h-caldesmon, calponin) and late markers (SM myosins, smoothelin) of VSMC differentiation. However, after blood vessel injury, surgery or explantation in vitro, VSMCs undergo a phenotypic modulation to synthetic phenotype, which endows them with high activity in migration, growth and proteosynthesis. These features can lead to stenosis or to obliteration of the vascular lumen and impaired blood supply to various tissues and organs
Vascular Smooth Muscle Cells (VSMCs) in Blood Vessel Tissue Engineering: The Use of Differentiated Cells or Stem Cells as VSMC Precursors
Vascular smooth muscle cells (VSMCs) play important roles in the physiology and pathophysiology of the blood vessels. In a healthy adult organism, VSMCs are quiescent, but after a blood vessel injury, they undergo phenotypic modulation from the contractile phenotype to the synthetic phenotype, characterized by high activity in migration, proliferation and proteosynthesis. This behavior of VSMCs can lead to stenosis or obliteration of the vascular lumen. For this reason, VSMCs have tended to be avoided in the construction of blood vessel replacements. However, VSMCs are a physiological and the most numerous component of blood vessels, so their presence in novel advanced vascular replacements is indispensable. Either differentiated VSMCs or stem cells as precursors of VSMCs can be used in the reconstruction of the tunica media in these replacements. VSMCs can be obtained from blood vessels (usually from subcutaneous veins) taken surgically from the patients and can be expanded in vitro. During in vitro cultivation, VSMCs lose their differentiation markers, at least partly. These cells should therefore be re-differentiated by seeding them on appropriate scaffolds by composing cell culture media and by mechanical stimulation in dynamic bioreactors. Similar approaches can also be applied for differentiating stem cells, particularly adipose tissue-derived stem cells, toward VSMCs for the purposes of vascular tissue engineering
Trait impulsivity in Juvenile Myoclonic Epilepsy
Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta‐analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs)
Sex-specific disease modifiers in juvenile myoclonic epilepsy
Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation
SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy
Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10−9) and 10p11.21 (P = 3.6 × 10−8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10−3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10−3) and increased seizure-like events (P = 6.8 × 10−7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10−3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease
Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly