Proteomics

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Proteomic and metabolomic profiling in human peripartum cardiomyopathy


ABSTRACT: Pregnancy imposes significant cardiovascular adaptations including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM have not been extensively examined in human hearts. We examined protein and metabolite expression in PPCM compared to familial dilated cardiomyopathy (DCM) and non-failing donors using unbiased quantitative mass spectrometry. Proteomics analysis identified uniquely downregulated proteins, such as SBSPON and TNS3, in PPCM relative to both DCM and donors. KEGG analysis of PPCM proteins identified key pathways associated with intracellular signalling cascades, protein folding and neurohormonal pathways that can directly impact the contractility of the heart. Metabolomics demonstrated uniquely expressed metabolites, such as upregulated homogentisate and deoxycholate, and downregulated lactate and alanine, along with reduced alanine, aspartate and glutamate metabolism are involved in the PPCM phenotype. Therefore, this study is the first to isolate unique molecular features underlying PPCM at the protein and metabolite level which may hold promise as future therapeutic candidate targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

SUBMITTER: David James  

LAB HEAD: Sean Lal

PROVIDER: PXD055986 | Pride | 2025-05-07

REPOSITORIES: Pride

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Publications

Myocardial Posttranscriptional Landscape in Peripartum Cardiomyopathy.

Li Amy A   Fang Bernard B   Li Mengbo M   Koay Yen Chin YC   Malecki Cassandra C   Hunter Benjamin B   Harney Dylan D   Dos Remedios Cristobal G CG   Larance Mark M   O'Sullivan John F JF   Lal Sean S  

Circulation. Heart failure 20241108 12


<h4>Background</h4>Pregnancy imposes significant cardiovascular adaptations, including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period, manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM hav  ...[more]

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