- Receptor Mechanisms and Signaling
- Coronary Interventions and Diagnostics
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Renin-Angiotensin System Studies
- Mesenchymal stem cell research
- Electrospun Nanofibers in Biomedical Applications
- Protease and Inhibitor Mechanisms
- Tissue Engineering and Regenerative Medicine
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Aortic Disease and Treatment Approaches
- Cardiomyopathy and Myosin Studies
- Cardiac Ischemia and Reperfusion
- Protein Kinase Regulation and GTPase Signaling
- Aortic aneurysm repair treatments
- Blood Coagulation and Thrombosis Mechanisms
- Cardiac Valve Diseases and Treatments
- Cardiac and Coronary Surgery Techniques
- Venous Thromboembolism Diagnosis and Management
- Telomeres, Telomerase, and Senescence
- Advanced biosensing and bioanalysis techniques
- TGF-β signaling in diseases
- Signaling Pathways in Disease
- Nitric Oxide and Endothelin Effects
- Atherosclerosis and Cardiovascular Diseases
Instituto do Coração
2004-2023
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2004-2023
Universidade de São Paulo
2012-2021
Harvard University
2015-2018
Massachusetts Institute of Technology
2015-2018
Brigham and Women's Hospital
2018
Universidade Federal de São Paulo
2000
University of Copenhagen
1997
Mesenchymal stem cells (MSCs) have been considered for human regenerative therapy applications, and safe culture expansion protocols are needed especially in the context of interspecies contamination. Human platelet lysate (PL) has proposed as animal serum substitute during vitro MSC expansion. In this work, a simplified efficient method to obtain autologous PL replace cell applications is described.PL obtained by freezing centrifugation procedures was tested medium supplement adipose...
It has been demonstrated that human adipose tissue-derived mesenchymal stem cells (hASCs) enhance vascular density in ischemic tissues, suggesting they can differentiate into or release angiogenic factors may stimulate neoangiogenesis. Moreover, there is evidence shear stress (SS) activate proliferation and differentiation of embryonic endothelial precursor (ECs). In this work, we investigated the effect laminar SS promoting hASCs ECs. (10 dyn/cm(2) up to 96 h), produced by a cone plate...
Abstract The rate of the remodeling arterialized saphenous vein conduit limits outcomes coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested hypothesis that high stretch (HS) induces human cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin VCAM1) THP-1 adhesion. decreases F-actin hSVECs, but not...
Two nonpeptide ligands that differ chemically by only a single methyl group but have agonistic (L-162,782) and antagonistic (L-162,389) properties <i>in vivo</i> were characterized on the cloned angiotensin AT<sub>1</sub> receptor. Both compounds bound with high affinity (<i>K</i><sub><i>I</i></sub> = 8 28 nm, respectively) to receptor expressed transiently in COS-7 cells as determined radioligand competition assays. L-162,782 acted powerful partial agonist, stimulating phosphatidylinositol...
Mechanotransduction enables cells to sense and respond stimuli, such as strain, pressure shear stress (SS), critical for maintenance of cardiovascular homeostasis or pathological states. The angiotensin II type 1 receptor (AT1R) was the first G protein-coupled described display stretch-induced activation in cardiomyocytes independent its ligand Ang II. Here, we assessed whether SS (15 dynes/cm2, 10 min), an important mechanical force present system, activates AT1R ligand. induced...
Abstract Smooth muscle cell (SMC) contractility is essential to vessel tone maintenance and blood pressure regulation. In response vasoconstrictors, calcium-dependent mechanisms promote the activation of regulatory myosin light chain, leading increased cytoskeleton tension that favors shortening. contrast, SMC maintain an intrinsic level a contractile force independent vasoconstrictor stimulation sustained contraction beyond timescale suggesting involvement additional players in response....
Aortic dissection is a life-threatening condition with complex immunological underpinnings. This study was aimed at exploring the causal relationships among immune cells, inflammatory proteins, and aortic dissection, through Mendelian randomization analysis. We used two-step approach to assess potential mediators, focusing on roles of blood cells proteins. analyzed GWAS data for 731 cell traits, 91 dissection. Single-nucleotide polymorphisms were as instrumental variables, analyses conducted...
The dynamic behavior of proteins within cellular structures can be studied using fluorescence recovery after photobleaching (FRAP) and loss (FLAP) experiments. These techniques provide insights into molecular mobility by estimating parameters such as turnover rates <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m1"><mml:mrow><mml:mo...
AimsCysteine- and glycine-rich protein 3/muscle LIM-domain (CRP3/MLP) mediates protein–protein interaction with actin filaments in the heart is involved muscle differentiation vascular remodelling. Here, we assessed induction of CRP3/MLP expression during arterialization human rat veins.
Adipose tissue-derived stem cells (ASCs) are among the more attractive adult cell options for potential therapeutic applications. Here, we studied and compared basic biological characteristics of ASCs isolated from humans (hASCs) mice (mASCs) maintained in identical culture conditions, which must be examined prior to considering further clinical hASCs mASCs were immunophenotype, differentiation potential, growth characteristics, senescence, nuclear morphology, DNA content. Although both...
We and others have previously demonstrated that adipose-derived stem cells (ASCs) transplantation improve cardiac dysfunction post-myocardium infarction (MI) under hemodynamic stress in rats. The beneficial effects appear to be associated with pleiotropic factors due a complex interplay between the transplanted ASCs microenvironment absence of cell transdifferentiation. In present work, we tested hypothesis mechanical stretch per se could change human (hASCs) into cardiovascular phenotypes...
Objectives We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser1270 are involved in shear-stress (SS)-induced downregulation the enzyme. Methods Results Western blotting analysis showed that SS (18 h, 15 dyn/cm2) decreases ACE expression as well p-JNK inhibition human primary endothelial cells (EC). CHO expressing wild-type (wt-ACE) also displayed SS-induced decrease p-JNK. Moreover, decreased promoter activity wt-ACE, but had no effect wild type or without either...
Abstract Mitochondria are dynamic organelles that change morphology to adapt cellular energetic demands under both physiological and stress conditions. Cardiomyopathies neuronal disorders associated with structure-related dysfunction in mitochondria, but three-dimensional characterizations of the still lacking. In this study, we combined high-resolution imaging 3D electron density information provided by cryo-soft X-ray tomography characterize mitochondria cristae isolated from murine. Using...
Summary Neo‐intima development and atherosclerosis limit long‐term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, key molecular events during arterialization resemble human adaptation. Right jugular was surgically connected to carotid artery observed up 90 days. Morphometry demonstrated gradual thickening medial layer important formation...
Rapamycin, the macrolide immunosuppressant and active pharmaceutic in drug-eluting stents (DES), has a well-recognized antiproliferative action that involves inhibition of mTOR pathway after binding to cytosolic protein FKBP12. TGF receptor-type I (TGFRI) spontaneous activation is inhibited by association with We hypothesized rapamycin, addition signaling, activates TGFRI independent TGFβ. Human umbilical vein endothelial cells (HUVECs) were treated rapamycin (10 nmol/l) and/or TGFβ RI...
Mechanical forces contribute to maintenance of cardiovascular homeostasis via the control release and production vasoactive substances. We demonstrated previously that shear stress decreases rat ACE activity expression. Using a reporter gene approach mutagenesis, we show now classic responsive element or SSRE (GAGACC) contained within 1,274 bp this promoter is not functional in response (15 dyn/cm2, 18 h) [for wild-type (WLuc), static (C) = 107 +/- 6.5%, (SS) 65.9 9.4%, n 8; for with mutated...
Saphenous vein grafting is still widely used to revascularize ischemic myocardium. The effectiveness of this procedure limited by neointima formation and accelerated atherosclerosis, which frequently leads graft occlusion. A better understanding process important clarify the mechanisms disease aid in formulation strategies for prevention and/or therapeutics.To develop an ex vivo flow system that allows controlled hemodynamics order mimic arterial venous conditions.Human saphenous veins were...
The role of different residues the rat AT 1A receptor in interaction with N‐ and C‐terminal ends angiotensin II (AngII) was studied by determining ligand binding production inositol phosphates (IP) COS‐7 cells transiently expressing following mutants: T88H, Y92H, G196I, G196W D278E. G196I retained significant IP‐production properties, indicating that bulky substituents position 196 did not affect AngII's carboxyl Lys 199 located three below. Although T88A mutation binding, T88H mutant had...
Patients with severe aortic stenosis have increased levels of prothrombotic and proinflammatory microparticles (MP), MPs actively regulate pathological processes that lead to atherothrombotic cardiovascular events. Shear stress is a validated stimulus MP production, abnormal shear in increases release ex-vivo studies. We hypothesized patients stenosis, percutaneous replacement the valve (TAVR) would reduce decrease circulating MPs.The experimental protocol utilized flow cytometry (FC)...