Membrane proteomic profiling of the heart: past, present, and future

Abstract

Cardiovascular diseases remain the most rapidly rising contributing factor of all-cause mortality and the leading cause of inpatient hospitalization worldwide, with costs exceeding $30 billion dollars annually in North America. Cell surface and membrane associated proteins play an important role in cardiomyocyte biology and are involved in the pathogenesis of many human heart diseases. In cardiomyocytes, membrane proteins serve as critical signaling receptors, Ca2+ cycling regulators, and electrical propagation regulators, all functioning in concert to maintain spontaneous and synchronous contractions of cardiomyocytes. Membrane proteins are excellent pharmaceutical targets due to their uniquely exposed position within the cell. Perturbations in cardiac membrane protein localization and function have been implicated in the progression and pathogenesis of many heart diseases. However, previous attempts at profiling the cardiac membrane proteome have yielded limited results due to poor technological developments for isolating hydrophobic, low abundant membrane proteins. Comprehensive mapping and characterization of the cardiac membrane proteome thereby remains incomplete. This review will focus on recent advances in mapping the cardiac membrane proteome and the role of novel cardiac membrane proteins in the healthy and diseased heart.

Multi‐omic analyses and network biology in cardiovascular disease

“…Moreover, while cardiac membrane proteins play critical roles in regulating cardiac cell function, comprehensive studies of these proteins have proven difficult given their hydrophobic nature and lower abundance (as we have previously reviewed in ref. [54]). Recent cardiac membrane protein targeted analyses, using general membrane isolation via centrifugation, have identified novel proteins at the cardiomyocyte intercalated disc [55], an important sub‐cellular domain of PPIs enabling electrical and mechanical coupling across adjacent myocytes.…”

Capture of the Mouse Organ Membrane Proteome Specificity in Peptidisc Libraries

“…The precise knowledge of these organ-specific proteins, whose expression is significantly elevated in a given organ, holds great medical significance. For instance, several clinical diagnostics rely upon organ-specific protein biomarkers to monitor pathological states and disease progression, whereas the development of therapeutics critically depends on understanding organ specificity to prevent cross-reactivity. , This knowledge is especially important at the cell surface since about two-thirds of the druggable proteome comprises integral membrane proteins. , Perturbation of the membrane proteome is also linked to neurodegenerative diseases, cancer, and disorders like hypertension and muscular dystrophy. − Genomic and transcriptomic technologies have undeniably proven their worth by shedding light on organ protein expression patterns. − Still, to achieve a comprehensive understanding of organ biology at a molecular level, a direct estimate of its protein content is imperative. − …”

Effectiveness of food concentrate phenolic compounds of apples in experimental membrane pathologies

“…Cell membrane damage is considered to be one of the leading links in the pathogenesis of many diseases (Mesa-Herrera et al, 2019;Cheng et al, 2020;Maciejowski et al, 2020;Lee et al, 2021). Membrane pathologies are a range of disorders that can be inherited or acquired (Risinger & Kalfa, 2020).…”