ENZYMES, GGROWTH FACTORS, PROTEINS, AND RECEPTORS

Wuchereria bancrofti

What lymphatic filarial parasite is also known as Bancroft’s filarial worm?

Brugia malayi

What lymphatic filarial parasite is also known as Malayan filarial worm?

Albendazole

What drug is donated by GlaxoSmithKline (GSK) for lymphatic filariasis (LF) elimination?

Diethylcarbamazine (DEC)

What drug is donated by Eisai Pharmaceuticals of Japan for LF elimination?

Ivermectin

What drug is donated by Merck and Company for LF elimination?

Titin

What is the largest protein expressed in humans, encoded by the TTN gene?

Titin

What protein spans the entire length of the sarcomere, connecting the Z and M-bands?

Titin

What protein functions as a molecular spring in myocytes?

Titin

What protein's dysfunction leads to dysfunction in the contractility of the muscle in dilated cardiomyopathy (DCM)?

Myosin-binding protein C (MYBP-C)

What sarcomeric protein's mutation is commonly found in hypertrophic cardiomyopathy (HCM)?

Beta-myosin heavy chain (beta-MHC)

What sarcomeric protein's mutation is commonly found in HCM?

Cardiac Troponin (TnI, TnT)

What sarcomeric protein's mutation is commonly found in HCM?

Alpha-tropomyosin

What sarcomeric protein's mutation is commonly found in HCM?

Dystrophin

What membrane-associated protein's mutation is associated with X-linked cardiomyopathies?

Dystrophin

What protein is associated with total or partial loss in Becker and Duchenne's muscular dystrophy?

Neutrophils

What immune cells are the primary target of ANCA antibodies?

Myeloperoxidase (MPO)

What lysosomal granule constituent is involved in generating oxygen free radicals, and is the target of MPO-ANCA?

Proteinase-3 (PR3)

What neutrophil azurophilic granule constituent is the target of PR3-ANCA?

Collagen

What extracellular matrix (ECM) protein is synthesized by vascular smooth muscle cells (SMCs)?

Elastin

What extracellular matrix (ECM) protein is synthesized by vascular smooth muscle cells (SMCs)?

Proteoglycans

What extracellular matrix (ECM) protein is synthesized by vascular smooth muscle cells (SMCs)?

Vascular Cell Adhesion Molecule-1 (VCAM-1)

What adhesion molecule on endothelial cells binds to monocytes and T lymphocytes early in atherogenesis?

Intercellular Adhesion Molecule-1 (ICAM-1)

What adhesion molecule on dysfunctional endothelial arterial cells is part of the mechanism for enhanced leukocyte adhesion?

Transforming Growth Factor-beta (TGF-beta)

What signaling pathway regulates the network of transcription factors essential for proper cardiac transformation?

Transforming Growth Factor-beta (TGF-beta)

What substance's signaling is dysregulated by Fibrillin-1 defects, causing structural laxity and myxomatous change in mitral valve prolapse?

Fibrillin-1 (FBN-1)

What protein's gene mutation causes Marfan syndrome, often associated with mitral valve prolapse?

Titin Gene (TTN)

What gene mutation, encoding the largest human protein, is the most common genetic alteration in dilated cardiomyopathy (DCM)?

Laminin A/C

What nuclear envelope protein's encoding gene can be mutated in familial dilated cardiomyopathy (DCM)?

Growth promoters and inhibitors

What two types of substances regulate the migratory and proliferative activities of vascular smooth muscle cells (SMCs)?

Growth factors and cytokines

What two types of molecules do vascular smooth muscle cells (SMCs) elaborate?

Collagen, elastin, and proteoglycans

What three components of the extracellular matrix (ECM) are synthesized by smooth muscle cells?

Vascular endothelial growth factor (VEGF), Bone morphogenetic protein, Transforming growth factor-beta (TGF-beta), WNT, Hedgehog, and Notch pathways

What six signaling pathways regulate the network of transcription factors essential for proper cardiac transformation?

Platelet-derived growth factor receptor (PDGFR) alpha or beta genes

What two genes are associated with chromosomal rearrangements in the myeloproliferative disorder linked to Loeffler endomyocarditis?

Major basic protein (MBP)

What toxic product of eosinophil granules is released, leading to endomyocardial necrosis in Loeffler endomyocarditis?

G protein alpha subunit (Gs-alpha)

What protein is encoded by the GNAS1 gene, which has activating mutations associated with familial syndromes linked to myxomas?

Regulatory subunit of a cyclic-AMP-dependent protein kinase

What protein is encoded by the PRKAR1A gene, which has null mutations associated with myxomas in the Carney complex?

Interleukin-6 (IL-6)

What cytokine's production is associated with a syndrome of constitutional symptoms in myxomas?

Matrix metalloproteinases (MMPs)

What enzymes, produced by inflammatory cell infiltrates (e.g., macrophages) in the arterial wall, lead to increased proteolysis of extracellular matrix proteins in the pathogenesis of abdominal aortic aneurysm (AAA)?

CD4+ T-cells

What immune cells, specific for streptococcal peptides, react with self-proteins in the heart to produce cytokines that activate macrophages in rheumatic fever (RF)?

Macrophages

What immune cells are activated by cytokines produced by CD4+ T-cells in rheumatic fever (RF)?

Anitschkow cells

What is another name for activated macrophages found in Aschoff bodies in rheumatic fever (RF)?

CD4+ T-cells

What immune cells infiltrate the temporal artery, driving subsequent proinflammatory cytokine production (e.g., TNF) in giant cell arteritis?

TNF

What proinflammatory cytokine is produced by activated T-cells and contributes to the pathogenesis of giant cell arteritis?

Anti-endothelial cell antibodies and anti-smooth muscle cell antibodies

What two types of antibodies are demonstrated in giant cell arteritis?

Elastin

What protein's gene deletion on chromosome 7 is associated with supravalvular aortic stenosis as a component of Williams-Beuren syndrome?

Elastin

What protein's gene mutation may cause supravalvular stenosis through disruption of its interaction with smooth muscle cells during aortic morphogenesis?

NKX2.5 and GATA4

What two transcription factors' mutations are associated with Atrial Septal Defect (ASD)?

NKX2.5 and ZFPM2

What two transcription factors' mutations are associated with Tetralogy of Fallot (TOF)?

NOTCH1

What gene mutation in the Notch pathway causes bicuspid aortic valve?

JAG1 or NOTCH2

What two gene mutations in the Notch pathway cause Tetralogy of Fallot (TOF)?

Fibrillin

What gene's mutations, associated with the Notch pathway, cause Marfan syndrome?

TBX1 transcription factor gene

What gene's deletion is the probable culprit in DiGeorge syndrome?

Plakoglobin

What desmosome-associated protein's gene mutation is specifically associated with Naxos syndrome?

TSC1 or TSC2 tumor suppressor genes

What two genes' mutations are associated with 50% of cardiac rhabdomyomas (the most frequent primary pediatric heart tumor)?

Myeloperoxidase (MPO)

What antigen is associated with MPO-ANCA (previously p-ANCA)?

Proteinase-3 (PR3)

What antigen is associated with PR3-ANCA (previously c-ANCA)?

Anti-myeloperoxidase ANCA (MPO-ANCA)

What specific antibody is characteristic of Microscopic polyangiitis?

Anti-myeloperoxidase ANCA (MPO-ANCA)

What specific antibody is characteristic of Churg-Strauss syndrome (Eosinophilic granulomatosis with polyangiitis)?

Anti-proteinase-3 ANCA (PR3-ANCA)

What specific antibody is characteristic of Granulomatosis with polyangiitis (Wegener's granulomatosis)?

Anti-endothelial cell antibodies

What antibodies are associated with vasculitis in Kawasaki disease?

CD31

What endothelial cell marker is used for immunohistochemical staining to prove the endothelial nature of angiosarcoma tumor cells?

Norepinephrine

What chemical is released by adrenergic cardiac nerves of the autonomic nervous system to increase heart rate, myocardial contractility, and vascular resistance?

Catecholamines

What substance is synthesized from the adrenal medulla and is released to increase heart rate, myocardial contractility, and vascular resistance?

Atrial Natriuretic Peptide (ANP)

What substance counterbalances the Renin-Angiotensin-Aldosterone System (RAAS) through diuresis and vascular smooth muscle relaxation?

Renin-Angiotensin-Aldosterone System (RAAS)

What system is activated by diminished renal perfusion in left-sided heart failure (LSHF) as a compensatory mechanism?

Beta-adrenergic receptors

What receptors' activation mediates trophic signals that contribute to cardiac hypertrophy?

Actin

What is the thin filament in the sarcomere (the basic contractile unit of the muscle)?

Myosin

What is the thick filament in the sarcomere (the basic contractile unit of the muscle)?

Alpha-helices

What is the typical form of amyloid proteins before they are deposited into organs?

Beta-pleated sheets

What insoluble structure do amyloid proteins form when deposited into different organs in amyloidosis?

Transthyretin

What protein are deposits in senile cardiac amyloidosis largely composed of, which accelerates amyloid deposition?

CD4+ T-cells

What cells in rheumatic fever react with self-proteins in the heart and produce cytokines that activate macrophages (Anitschkow cells)?

M proteins

What specific proteins of streptococci are targeted by antibodies that cross-react with self-antigens in the heart in rheumatic fever?

Streptolysin O and DNase B

What two streptococcal enzymes are targeted by antibodies seen in the serum of a patient with rheumatic fever?

Tissue factor

What procoagulant is associated with mucinous adenocarcinomas and may relate to the systemic hypercoagulable state seen in Nonbacterial Thrombotic Endocarditis (NBTE)?

Vascular cell adhesion molecule-1 (VCAM-1)

What is the ligand for the VLA-4/beta 1 integrin, and is expressed on dysfunctional endothelial arterial cells?

Intercellular adhesion molecule-1 (ICAM-1)

What is the ligand for the LFA-1 and Mac-1/beta 2 integrins, and is expressed on dysfunctional endothelial arterial cells?

Integrins

What molecules on white blood cells (WBCs) mediate firm adhesion to the endothelium, binding to VCAM-1 and ICAM-1?

Monocytes and T lymphocytes

What two types of white blood cells does VCAM-1 bind to early in atherogenesis?

Myeloperoxidase (MPO)

What lysosomal granule constituent is involved in generating oxygen free radicals?

Proteinase-3 (PR3)

What neutrophil azurophilic granule constituent is associated with Granulomatosis with polyangiitis (GPA)?

Beta-adrenergic blockade

What pharmacologic intervention decreases heart rate and contractility to help patients with hypertrophic cardiomyopathy (HCM)?

Imatinib

What tyrosine kinase inhibitor treats patients with myeloproliferative disorder associated with chromosomal rearrangements of PDGFR genes, sometimes reversing Loeffler endomyocarditis?

Plakoglobin

What desmosome-associated protein is associated with defective cell adhesion in arrhythmogenic right ventricular cardiomyopathy (ARVC)?

Gsα

What subunit of G protein is encoded by the GNAS1 gene, associated with myxomas?

Elastin

What extracellular matrix protein is degraded by Matrix Metalloproteinases (MMPs) in the pathogenesis of AAA?

Collagen

What extracellular matrix protein is degraded by Matrix Metalloproteinases (MMPs) in the pathogenesis of AAA?

Proteoglycans

What extracellular matrix protein is degraded by Matrix Metalloproteinases (MMPs) in the pathogenesis of AAA?

Laminin

What extracellular matrix protein is degraded by Matrix Metalloproteinases (MMPs) in the pathogenesis of AAA?

Fibronectin

What extracellular matrix protein is degraded by Matrix Metalloproteinases (MMPs) in the pathogenesis of AAA?

Endothelial cell marker CD31

What immunohistochemical marker proves the endothelial nature of angiosarcoma tumor cells?

TNF

What proinflammatory cytokine is involved in the T-cell mediated immune response in Giant Cell Arteritis?

beta-adrenoceptors

What receptors, when activated, mediate trophic signals that lead to cardiac hypertrophy?

beta-adrenoceptors

What receptors are targeted by beta-adrenergic blockade to decrease heart rate and contractility in HCM?

Hedgehog

What signaling pathway regulates transcription factors essential for proper cardiac transformation?

WNT

What signaling pathway regulates transcription factors essential for proper cardiac transformation?

Notch pathways

What signaling pathway mutations cause bicuspid aortic valve and Tetralogy of Fallot?

Fibroblast growth factor

What signaling pathway regulates transcription factors essential for proper cardiac transformation?

Atrial Natriuretic Peptide (ANP)

What is released to cause diuresis, natriuresis, and vasodilation to counterbalance the RAAS?

Eosinophil granule

What is the source of Major Basic Protein (MBP)?