Posts Tagged: heart

AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System

AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System

Ian P. Salt, D. Grahame Hardie

Structure of human AMP-activated protein kinase (AMPK; α1β2γ1 complex).8 The model was created in space-filling mode using PyMol v1.7.4.2 with the co-ordinates in PDB file 4RER and with color coding similar to that in Figure 1. The heterotrimer was crystallized in the presence of β-cyclodextrin, which occupies the glycogen-binding site, staurosporine, which occupies the active site, and AMP, which occupies sites 1, 3, and 4 on the γ subunit (sites 1 and 4 are round the back in this view). Although Thr172 was phosphorylated, it is not visible in this view but lies in the cleft between the kinase domain C lobe and the β-CTD, just over the right-hand shoulder of the C-lobe. ADaM indicates Allosteric Drug and Metabolite; AID, autoinhibitory domain; CBM, carbohydrate-binding module; CBS1, cystathionine beta-synthase motif-1, etc; CTD, C-terminal domain; and NTD, N-terminal domain. [Powerpoint File]

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease

Damien P. Kenny, Ziyad M. Hijazi

Cartoon illustrating possible future strategies for the surgical management of newborns with congenital heart disease (CHD). If CHD is diagnosed prenatally, fetal cells may be harvested and induced pluripotent stem cells (iPS) generated; as an alternative, umbilical cord stem cells can be isolated at the time of birth. When diagnosis of CHD is made after birth or in babies who require a palliative surgical operation soon after birth, stem cells may be isolated from surgical cardiac leftovers. All these types of cells will allow the generation of a tissue-engineered graft endowed with growth and remodeling potential, necessary for the definitive correction of cardiac defects (Taken from Avolio et al99; Illustration Credit: Ben Smith). [Powerpoint File]

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease

Damien P. Kenny, Ziyad M. Hijazi

Series of angiographic images demonstrating hybrid pulmonary valve replacement after plication of the main pulmonary artery in a patient with a significantly dilated right ventricular outflow tract (RVOT) after transannular patch repair of tetralogy of Fallot as an infant. A and B, Initial angiogram demonstrating dilated RVOT measuring 33 mm; (C) RVOT angiogram after main pulmonary artery (MPA) plication and placement of a prestent; and (D) MPA angiogram demonstrating valvular competence with no pulmonary incompetence after Melody valve placement. [Powerpoint File]

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease

Damien P. Kenny, Ziyad M. Hijazi

Series of fetal echocardiography images demonstrating fetal aortic balloon valvuloplasty. A, Initial fetal echocardiogram demonstrating dilated left ventricle (LV) with narrow color jet seen across stenotic aortic valve; (B) introduction of needle into the cavity of the LV (white arrow signifies needle tip); (C) wire seen crossing the aortic valve (white arrow); and (D) inflation of balloon across the aortic valve (white arrow). [Powerpoint File]

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

Anton V. Borovjagin, Brenda M. Ogle, Joel L. Berry, Jianyi Zhang

Bioprinting is usually accomplished using a combination of gel and cells. Laser-assisted bioprinting (A) using Laser-induced forward transfer relies on the focused energy of a laser onto an energy absorbing ribbon to induce bioink droplet formation. This technique is advantageous because it avoids the problem of clogging of the bioink nozzle that plagues other bioprinting techniques. Multiphoton excitation-based printing (B) is accomplished via photocrosslinking of proteins or polymers in the focal volume of the laser and excels in its high resolution and ability to polymerize many native proteins that do not form hydrogels spontaneously outside the body. Inkjet printing (C), one of the most common printing techniques, relies on a vapor bubble or a piezoelectric actuator to displace material to extrude the bioink from a nozzle. Robotic dispensing (D) uses other mechanical means of displacing bioink under robotic control. ECM indicates extracellular matrix. [Powerpoint File]

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

From Microscale Devices to 3D Printing: Advances in Fabrication of 3D Cardiovascular Tissues

Anton V. Borovjagin, Brenda M. Ogle, Joel L. Berry, Jianyi Zhang

In vitro testing of cells and tissues may occur in several ways. Microfluidic systems (A) have emerged as a tool for basic science studies of the effect of highly controlled fluid mechanical and solid mechanical forces on single cell types or cocultures. Microfluidic systems are also gaining favor as a diagnostic tool and a platform for drug development. Organoid cultures (B) are described as organ buds grown in culture that feature realistic microanatomy and are useful as cellular models of human disease. These cultures have found utility in the study of basic mechanisms of organ-specific diseases. Spheroid cultures (C) feature sphere-shaped clusters of a single cell type or coculture sustained in a gel or a bioreactor in order to interact with their 3D surroundings and are useful in testing drug efficacy and toxicity. (D) Engineered heart tissues are constructed by polymerizing an extracellular matrix–based gel containing cardiac cell types between 2 elastomeric posts or similar structures allowing auxotonic contraction of cardiomyocytes. This allows approximation of the normal conditions of the heart contracting against the hydrostatic pressure imposed by the circulation. This type of tissue construct has been used for testing toxicity of drugs and basic studies of muscle function and interplay between multiple cardiac cell types. [Powerpoint File]

The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms

The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms

Jason Roh, James Rhee, Vinita Chaudhari, Anthony Rosenzweig

Multiple mechanisms have been proposed for impaired cardiomyocyte function observed in aging, and how exercise partially reverses their effects. (1) Diminished cardiac performance in the pathological hypertrophy of aging is linked to decreased insulin-like growth factor-I (IGF-I)–phosphatidylinositol 3-kinase (PI3K)–AKT and β-adrenergic receptor (β-AR)–cAMP–protein kinase A (PKA) signaling, decreased sarcoplasmic reticulum Ca2+–ATPase2a (SERCA2a) expression and activity and inefficient calcium handling, and mitochondrial dysfunction secondary to excessive reactive oxygen species (ROS). (2) Exercise confers physiological hypertrophy and cardioprotection in the form of enhanced β-adrenergic and IGF-1 signaling, SERCA2a activity and calcium handling, and mitochondrial dynamics, the latter mediated largely through peroxisome proliferator-activated receptor γ coactivator (PGC)-1α. (3) These benefits of exercise potentially mitigate the effects of aging (Illustration Credit: Ben Smith). [Powerpoint File]

Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis

Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis

Cassandra L. Happe, Adam J. Engler

Interplay of chemical and mechanical signals that underlie cardiac specification and development. Schematic representation of integrin-mediated signaling specifically detailing how chemical signals (left), for example, integrin ligation, drive focal adhesion formation, and downstream events leading to transcriptional changes. Mechanical signals (right) are mediated by actomyosin contractions. Both influence transcriptional changes via common mechanisms diagrammed at the bottom of the illustration, including chromatin remodeling and changes in nuclear pore complex diffusion among others. Dash and solid lines indicate the direction of biophysical and biochemical interactions, respectively. AKT indicates protein kinase B; ECM, extracellular matrix; FAK, focal adhesion kinase; GSK, glycogen synthase kinase; ILK, integrin-linked kinase; and PI3K, phosphoinositide 3-kinase. [Powerpoint File]

Mechanotransduction in Cardiac Hypertrophy and Failure

Mechanotransduction in Cardiac Hypertrophy and Failure

Robert C. Lyon*, Fabian Zanella*, Jeffrey H. Omens, Farah Sheikh

A schematic representation of the specific protein complexes linked to sarcomere-mediated mechanotransduction and mechanotransmission in cardiac muscle. CnA indicates calcineurin A; CS-1, calsarcin-1; ECM, extracellullar matrix; ERK2, extracellular signal–regulated kinase-2; FHL1, four-and-a-half LIM domain protein 1; MARPs, muscle-specific ankyrin repeat proteins; MEK2, mitogen-activated protein kinase kinase-2; MLP, muscle-specific LIM domain protein; MURFs, muscle-specific RING-finger proteins; NBR1 indicates neighbor to BRCA1; N-RAP, nebulin-related anchoring protein; p62/SQSTM1, p62/sequestosome-1; PICOT, protein kinase C–interacting cousin of thioredoxin; RAF1, rapid accelerated fibrosarcoma-1; and TCAP, titin Cap (illustration credit: Ben Smith). [Powerpoint File]

Mechanotransduction in Cardiac Hypertrophy and Failure

Mechanotransduction in Cardiac Hypertrophy and Failure

Robert C. Lyon*, Fabian Zanella*, Jeffrey H. Omens, Farah Sheikh

A schematic representation of the specific protein complexes linked to cell–cell junction and sarcolemma-mediated mechanotransduction and mechanotransmission in cardiac muscle. Dotted arrows highlight cross-talk between integrin and caveolin, as well as integrin and the dystroglycan complex. α-CAT indicates α-catenin; β-CAT, β-catenin; CAR, coxsackievirus-associated receptor; CAS, p130 CRK-associated substrate; CAV3, caveolin-3; DSC2 indicates desmocollin-2; DSG2, desmoglein-2; DSP, desmoplakin; ECM, extracellullar matrix; FAK, focal adhesion kinase; ILK, integrin-linked kinase; JUP, plakoglobin; N-CAD, N-cadherin; PAX, paxilin; PKP2, plakophillin-2; and VIN, vinculin (illustration credit: Ben Smith). [Powerpoint File]

The Structural Factor of Hypertension: Large and Small Artery Alterations

The Structural Factor of Hypertension: Large and Small Artery Alterations

Stéphane Laurent, Pierre Boutouyrie

Schematic representation of the role of arterial stiffness in assuming blood flow through the peripheral circulation (Reprinted from Briet et al65 with permission). [Powerpoint File]

Molecular Mechanisms of Autophagy in the Cardiovascular System

Molecular Mechanisms of Autophagy in the Cardiovascular System

Damián Gatica, Mario Chiong, Sergio Lavandero, Daniel J. Klionsky

The 3 main types of autophagy. A, Yeast cells carry out both macroautophagy and microautophagy. Although macroautophagy consists of the bulk degradation of cytoplasmic material that is sequestered inside double-membrane autophagosomes that then fuse with the vacuole, microautophagy works by directly taking up the substrates through invagination of the vacuole. B, In mammals along with microautophagy and macroautophagy, chaperone-mediated autophagy enables the degradation of specific protein substrates that contain a KFERQ motif that is recognized by chaperones that mediate the translocation of the unfolded protein into the lysosome through LAMP2A. [Powerpoint File]

Molecular Mechanisms of Autophagy in the Cardiovascular System

Molecular Mechanisms of Autophagy in the Cardiovascular System

Damián Gatica, Mario Chiong, Sergio Lavandero, Daniel J. Klionsky

Autophagy regulation. Through serine/threonine kinase 11 (STK11/LKB1), AMP-activated protein kinase (AMPK) senses decreases in the ATP/AMP ratio and phosphorylates tuberous sclerosis (TSC) 1-TSC2, which then targets Ras homolog enriched in brain (RHEB), leading to mechanistic target of rapamycin complex 1 (MTORC1) inhibition and autophagy activation. insulin receptor/insulin-like growth factor 1 receptor (INSR/IGF1R) triggers the activation of the class I phosphoinositide 3-kinase (PI3K), inducing the formation of phosphatidylinositol(3,4,5)trisphosphate (PIP3) and AKT/PKB activation; AKT can inhibit TSC1-TSC2, blocking autophagy. Phosphatase and tensin homolog (PTEN) works as a PIP3 phosphatase generating phosphatidylinositol(4,5)bisphosphate (PIP2) and inducing autophagy. [Powerpoint File]

Molecular Mechanisms of Autophagy in the Cardiovascular System

Molecular Mechanisms of Autophagy in the Cardiovascular System

Damián Gatica, Mario Chiong, Sergio Lavandero, Daniel J. Klionsky

Autophagosomes have a diverse range of potential membrane sources. The trans-Golgi network, mitochondria, mitochondrial-associated membrane, and endoplasmic reticulum (ER) have been postulated as membrane donors. Omegasomes have been described as the ER structures that work as a platform for autophagosome formation. The phagophore (shown in red) elongates and engulfs part of a cisternae before it buds off the ER and becomes an autophagosome. MAM indicates mitochondria-associated ER membrane. [Powerpoint File]

Molecular Mechanisms of Autophagy in the Cardiovascular System

Molecular Mechanisms of Autophagy in the Cardiovascular System

Damián Gatica, Mario Chiong, Sergio Lavandero, Daniel J. Klionsky

Autophagy regulators in cardiomyocytes. A wide variety of stimuli can regulate autophagy in cardiomyocytes. Some of them are autophagy activators and are associated with cardiovascular diseases. However, acetylcholine, catecholamines, aging, insulin-like growth factor 1 (IGF1), and insulin (INS) are capable of inhibiting autophagy. INS and IGF1 are well-known cardioprotective agents. AchR indicates acetylcholine receptor; AGT II, angiotensin II; AGTR, angiotensin II receptor, type 1; IGF1R, IGF1 receptor; INSR1, INS receptor 1; and PKA, protein kinase A. [Powerpoint File]