Posts Tagged: cardiovascular disease

Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways

Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways

Dariush Mozaffarian, Jason H.Y. Wu

Selected cardiometabolic benefits of flavonoids and potential underlying molecular mechanisms. In vitro and animal studies support bioactivity of purified flavonoids or flavonoid-rich plant extracts across multiple tissues. Relevant molecular pathways seem to include (1) modulation of gene expression and signaling pathways. Enhancement of AMPK (5′-monophosphate-activated protein kinase) phosphorylation and activation appears to be a common mechanism affected by several types of flavonoids. Modulation of other signaling pathways has also been observed including increased expression of PPAR-γ (peroxisome proliferator-activated receptor-γ) and inhibition of NF-κB (nuclear factor-κB) activation; (2) interaction with gut microbiota. Dietary flavonoids may alter gut-microbial composition because of probiotic-like properties and stimulate growth of specific bacteria (eg, Akkermansia muciniphila) that may confer metabolic benefits. Conversely, metabolism of dietary flavonoids by gut bacteria generates downstream metabolites (eg, phenolic acids) that may possess unique properties and reach higher circulating and tissue concentrations compared with parent flavonoids, thus enhancing biological activity of flavonoids; (3) Direct flavonoid–protein interactions. Growing evidence suggests that flavonoids both stimulate and inhibit protein function, including of ion channels in the vasculature and liver and carbohydrate digestive enzymes (α-amylase and α-glucosidase) in the gastrointestinal tract. Such effects may partly contribute to regulation of vascular tone and glucose metabolism. ERK1/2 indicates extracellular signal-regulated kinases 1 and 2; GLUT4, glucose transporter type 4; IRS2, insulin receptor substrate-2; MAPK, mitogen-activated protein kinase; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; PKA; protein kinase-A; SREBP-1c, sterol regulatory element–binding protein-1c; TG, triglycerides; and TLR4, toll-like receptor 4. (Illustration Credit: Ben Smith.) [Powerpoint File]

Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways

Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways

Dariush Mozaffarian, Jason H.Y. Wu

Relevant characteristics of dairy foods and selected molecular pathways potentially linked to cardiometabolic disease risk. Dairy foods are characterized by a complex mixture of nutrients and processing methods that may influence cardiovascular and metabolic pathways. Examples of relevant constituents include specific fatty acids, calcium, and probiotics. Relevant processing methods may include animal breeding and feeding, fermentation, selection and cultivation of bacterial and yeast strains (eg, as fermentation starters), and homogenization. Such modifications can alter the food’s composition (eg, fermentation leads to production of vitamin K2 from vitamin K1) and its lipid structures (eg, homogenization damages MFGM), each of which can affect downstream molecular and signaling pathways. BCSFA indicates branched-chain saturated fats; GLP-1, glucagon-like peptide 1; MCSFA, medium-chain saturated fats; MFGM, milk-fat globule membranes; MGP, matrix glutamate protein; mTOR, mammalian target of rapamycin; and OCSFA, odd-chain saturated fats. (Illustration Credit: Ben Smith.) [Powerpoint File]

Somatic Mutations and Clonal Hematopoiesis: Unexpected Potential New Drivers of Age-Related Cardiovascular Disease

Somatic Mutations and Clonal Hematopoiesis: Unexpected Potential New Drivers of Age-Related Cardiovascular Disease

José J. Fuster, Kenneth Walsh

Somatic mutations in blood cells as a shared mechanism of hematologic cancer and cardiovascular disease. A, The accumulation of somatic mutations in hematopoietic progenitor and stem cells is an inevitable consequence of the process of aging. Some of these random mutations confer a competitive advantage to the mutant cells, leading to its clonal expansion. This phenomenon can be defined as somatic mutation-driven clonal hematopoiesis. B, Most individuals exhibiting somatic mutation-driven clonal hematopoiesis only carry 1 driver mutation (eg, in DNMT3A, TET2, ASXL1, or JAK2). Although this situation greatly increases the risk of acquiring additional driver mutations and eventually developing a hematologic cancer, this condition is infrequent, even in individuals with clonal hematopoiesis. The main cause of death in individuals exhibiting somatic mutation-driven clonal hematopoiesis is atherosclerotic cardiovascular disease. Grey shade in the figure indicates decreasing frequency. HSPC indicates hematopoietic stem/progenitor cell. [Powerpoint File]

Resident and Monocyte-Derived Macrophages in Cardiovascular Disease

Resident and Monocyte-Derived Macrophages in Cardiovascular Disease

Lisa Honold, Matthias Nahrendorf

Macrophage mediators and crosstalk after myocardial infarction. TNF-α (tumor necrosis factor α) acts on cardiomyocytes and can induce hypertrophy and cell death. TGF-β (transforming growth factor-β) induces conversion of fibroblasts to myofibroblasts that produce collagen necessary for scar formation. Proteolytic enzymes like MMPs (matrix metalloproteinases) contribute to tissue remodeling, whereas VEGF (vascular endothelial growth factor) acts on endothelial cells and stimulates angiogenesis. [Powerpoint File]

Resident and Monocyte-Derived Macrophages in Cardiovascular Disease

Resident and Monocyte-Derived Macrophages in Cardiovascular Disease

Lisa Honold, Matthias Nahrendorf

Macrophages in cardiovascular disease. During myocardial infarction (MI), atherosclerosis and stroke, monocytes are supplied by medullary and extramedullary hematopoiesis in bone marrow and spleen. Monocytes infiltrate diseased tissues, differentiate into macrophages and proliferate locally. In MI, resident cardiac macrophages are lost, whereas arterial macrophages in atherosclerosis persist. Cerebral microglia are activated after stroke and contribute to disease progression and healing. In obesity, macrophage accumulation in adipose tissue stems from local proliferation of resident and recruitment of monocyte-derived macrophages. [Powerpoint File]

Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases

Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases

Ji-Hye Jung, Xuebin Fu, Phillip C. Yang

Biogenesis of exosome. Exosomes are compartmentalized into the multivesicular bodies (MVBs), which fuse with the cell membrane and released to the extracellular space. This process prevents exosomes from degradation by the lysosomes. Exosomes comprise of various transmembrane and cytosolic proteins, such as integrins, CD9, CD63, and CD81. Furthermore, exosomes retain donor cells’ proteins, DNA fragments, miRNAs, and noncoding RNAs within the bilipid membrane. As such, exosomes preserve the genetic information of donor cells from enzymatic degradation while enabling targeted delivery of specific cargo. [Powerpoint File]

Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases

Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases

Ji-Hye Jung, Xuebin Fu, Phillip C. Yang

Exosomes mediated intercellular communication in heart. Exosomes facilitate communication among cardiomyocytes, endothelial cells, and vascular smooth muscle cells in the infarcted area of the heart. Exosomes transfer signaling molecules, such as miRNAs, mRNAs, and proteins to confer paracrine effects on the neighboring cells. In addition, pathological and physiological influence on the heart stimulates exosome secretion. Therefore, cardiac exosomes under pathological conditions could be used as ideal markers for diagnostic tools in the clinic. [Powerpoint FIle]

Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases

Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases

Ji-Hye Jung, Xuebin Fu, Phillip C. Yang

Personalized therapy with the exosomes generated from induced pluripotent stem cell (iPSC)–derived cardiomyocytes (iCMs). Exosomes from patient-specific iPSC derivatives provide a platform for personalized therapy by simulating endogenous repair. Exosomes can be directed to specific injured site of each individual patient to promote salvage of the existing injured cardiac cells. Exosomes isolated from the supernatant of iCM culture undergo ultracentrifugation methods, as well as advanced characterization and quantification by transmission electronical microscopy, Nanosight, and dynamic light scattering. [Powerpoint File]

Heart Failure Considerations of Antihyperglycemic Medications for Type 2 Diabetes

Heart Failure Considerations of Antihyperglycemic Medications for Type 2 Diabetes

Eberhard Standl, Oliver Schnell, Darren K. McGuire

Heart failure in type 2 diabetes mellitus: the ominous octet. CAD indicates coronary artery disease; CV, cardiovascular; and SNS, sympathetic nervous system. [Powerpoint File]

Mechanical Regulation of Cardiac Aging in Model Systems

Mechanical Regulation of Cardiac Aging in Model Systems

Ayla O. Sessions, Adam J. Engler

Physiological vs pathological age–related changes of the sarcomere and intercalated disc (ID). Schematic representation of sarcomere and ID components in the cardiomyocyte implicated in physiological aging (red, upregulated; green, downregulated), pathological aging (yellow, upregulated; blue, downregulated), or yet undetermined (black). Arrows to nucleus indicate translocation of protein into the nucleus with age. α-CAT indicates α-catenin; ACTN1, α-actinin-1; α-MHC, α-myosin heavy chain; β-CAT, β-catenin; c-TnT4, cardiac troponin T-4; F-actin, filamentous actin; MLP, muscle-binding limb protein; N-CAD, N-cadherin; P-MLC-2, phosphorylated myosin light chain-2; and Vinc, vinculin. [Powerpoint File]

Mechanical Regulation of Cardiac Aging in Model Systems

Mechanical Regulation of Cardiac Aging in Model Systems

Ayla O. Sessions, Adam J. Engler

Physiological vs pathological age–related changes of costamere and extracellular matrix (ECM). Schematic representation of Costamere and ECM of the cardiomyocyte implicated in physiological aging (red, upregulated; green, downregulated), pathological aging (yellow, upregulated; blue, downregulated), or yet undetermined (black). Stripes of 2 colors indicate lack of consensus on expression levels across species or involvement in physiological vs pathological aging. α7 indicates α7-integrin; β1, β1-integrin; ACTN1, α-actinin-1; AGE’s, advanced glycosylation endproducts; Col I, collagen type 1; Col IV, collagen type IV; F-actin, filamentous actin; ID, intercalated disc; ILK, integrin-linked kinase; MMP2, matrix mettaloproteinase-2; MMP9, matrix metalloproteinase-9; MMP14, matrix metalloproteinase-14; and Vinc, vinculin. [Powerpoint File]

Cardiovascular Disease in Women: Clinical Perspectives

Cardiovascular Disease in Women: Clinical Perspectives

Mariana Garcia, Sharon L. Mulvagh, C. Noel Bairey Merz, Julie E. Buring, JoAnn E. Manson

Traditional and nontraditional atherosclerotic cardiovascular disease (ASCVD) risk factors in women. Increasing among women and more impactful traditional ASCVD risk factors include diabetes mellitus, hypertension, dyslipidemia, smoking, obesity, and physical inactivity. Emerging, nontraditional ASCVD risk factors include preterm delivery, hypertensive pregnancy disorders, gestational diabetes mellitus, breast cancer treatments, autoimmune diseases, and depression. [Powerpoint File]

 

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Kathleen M. Broughton, Mark A. Sussman

Cardiac regenerative medicine product to marketplace. Several companies focused on the treatment of heart failure and regenerative cardiac medicine have emerged over the past decade. At this time, no commercially available product is approved by the US FDA and commercially available in the United States. Each company is positioned based on its most current clinical status in ClinicalTrials.gov and the company website. This figure was last updated on February 1, 2016. [Powerpoint File]

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps

Kathleen M. Broughton, Mark A. Sussman

Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of individual adult stems cells as a cardiovascular therapy. The analysis focus is the individual adult stem cell therapeutic treatment options. The analysis focuses on the internal workings of the individual treatment options based on current clinical trial results and ongoing preclinical research. [Powerpoint File]

Cyclic AMP Sensor EPAC Proteins and Their Role in Cardiovascular Function and Disease

Cyclic AMP Sensor EPAC Proteins and Their Role in Cardiovascular Function and Disease

Frank Lezoualc’h, Loubina Fazal, Marion Laudette, Caroline Conte

Mechanism of exchange protein directly activated by cAMP (EPAC) activation. cAMP is produced from ATP by adenylyl cyclase (AC) in response to Gαs-coupled G protein–coupled receptors (GPCRs) stimulation and activates its classical downstream effector, cAMP-dependent protein kinase A (PKA). Phosphodiesterases (PDE) degrade cAMP and thereby regulate the duration and intensity of cAMP signaling. EPAC function in a PKA-independent manner and represents a novel mechanism for governing signaling specificity within the cAMP cascade. Binding of cAMP to the high-affinity cyclic nucleotide–binding domain (CNBD-B) of EPAC induces marked conformational changes in the protein, which leads to exposure of the catalytic region for binding of Rap GTPase to catalyze the exchange of GDP for GTP. Rap-GTPase–activating proteins (Rap-GAPs) enhance the intrinsic GTP hydrolysis activity of Rap leading to GTPase inactivation. [Powerpoint File]