Table - PMC

. 2019 Jun 24;31(4):318–358. doi: 10.1089/ars.2017.7236

Table of Contents
I. Genotype–Phenotype Relationship in Hypertrophic Cardiomyopathy	319
II. Functional Defects Caused by Mutant Proteins Cannot Solely Account for HCM Progression	321
III. Toxic Dose of Mutant Protein	321
A. HCM allelic imbalance	322
B. Epigenetics	322
IV. Vicious Mutation-Induced Cycle	323
V. Direct Mutation Effects	324
VI. Metabolic Perturbations	326
VII. Myofilament Ca²⁺-Sensitization: Direct and Indirect Players	326
VIII. Decoupling Between the PCr-CK Pathway and Mitochondrial Oxidative Phosphorylation	329
IX. Oxidative Stress	330
X. Redox Signaling, Oxidative Stress, and Antioxidant Defense	330
A. Protein modifications	333
B. DNA damage	333
C. Lipid damage	333
XI. Oxidative Stress Markers in the Heart and Serum of HCM Patients	334
XII. Oxidative Stress Markers in HCM Animal Models	335
A. MYH mutations	335
B. MYBPC3 mutations	336
C. Tnnt2 mutations	337
D. Tpm1 mutations	338
XIII. Oxidative Stress as a Target for Therapy in HCM Animal Models	338
XIV. Antioxidant Enzymes in HCM Pathology	339
XV. How Sarcomeric Mutations and Secondary Disease Mechanisms Contribute to Excessive Levels of ROS and HCM Pathology	340
A. Cardiac mechanical stress	340
B. Mitochondrial activation alters the cardiac redox state	342
C. Mitochondrial damage	342
D. UPS dysfunction	342
E. Microvascular dysfunction	343
F. Myocardial fibrosis	343
G. Adrenergic and angiontensin II stimulation	343
XVI. Therapies	344
XVII. Restoring the Redox Balance as a Promising Therapeutic Approach in HCM Patients	344
A. Current HCM therapies	344
B. N-acetylcysteine	344
C. Peptide SS-31	344
D. Coenzyme Q	345
E. Estrogen	345
F. Metabolic therapies	345
G. XO inhibitor	345
XVIII. Breaking the Vicious Cycle	347