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Many proteins may undergo abnormal change in response to the stimulants, leading to regulation of posttranslationally modified proteins. In this review, the physiological and pathological roles of protein glycosylation in cardiac hypertrophy is discussed, and how the signal pathways regulate heart function and leading to heart failure. The analytical methods for analysis of protein glycosylation, including glycans, glycosite, occupancy, and heterogeneity is emphasized. The rationale on glycoproteins as disease biomarkers is also discussed. 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