Cardiac myosin-binding protein C as a biomarker of acute myocardial infarction

Marber, Michael; Mills, Nicholas L; Morrow, David A.; Müeller, Christian

doi:10.1093/ehjacc/zuab086

Cited by 8 publications

(3 citation statements)

References 5 publications

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“…Reports of determination of cMyBP-C and its fragments as a biomarker for cardiac disorders provide a proof of concept that determination of serum levels of S-glutathionylated cMyBP-C may be a biomarker with functional implications. Studies identified serum cMyBP-C as a biomarker of severe cardiovascular diseases and in acute myocardial infarction (77)(78)(79)(80). Based on our studies of S-glutathionylation of cMyBP-C in a model of diastolic dysfunction, Dudley and colleagues (81) further investigated changes in cMyBP-C in cardiac samples of mice fed on normal chow or a high fat diet (HFD) inducing diastolic dysfunction and insulin resistance.…”

Section: Potential Use Of S-glutathionylated Sarcomere Proteins As Bi...mentioning

confidence: 99%

Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis

Rosas¹,

Solaro

2023

Front. Cardiovasc. Med.

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The discovery that cardiac sarcomere proteins are substrates for S-glutathionylation and that this post-translational modification correlates strongly with diastolic dysfunction led to new concepts regarding how levels of oxidative stress affect the heartbeat. Major sarcomere proteins for which there is evidence of S-glutathionylation include cardiac myosin binding protein C (cMyBP-C), actin, cardiac troponin I (cTnI) and titin. Our hypothesis is that these S-glutathionylated proteins are significant factors in acquired and familial disorders of the heart; and, when released into the serum, provide novel biomarkers. We consider the molecular mechanisms for these effects in the context of recent revelations of how these proteins control cardiac dynamics in close collaboration with Ca2+ fluxes. These revelations were made using powerful approaches and technologies that were focused on thin filaments, thick filaments, and titin filaments. Here we integrate their regulatory processes in the sarcomere as modulated mainly by neuro-humoral control of phosphorylation inasmuch evidence indicates that S-glutathionylation and protein phosphorylation, promoting increased dynamics and modifying the Frank-Starling relation, may be mutually exclusive. Earlier studies demonstrated that in addition to cTnI as a well-established biomarker for cardiac disorders, serum levels of cMyBP-C are also a biomarker for cardiac disorders. We describe recent studies approaching the question of whether serum levels of S-glutathionylated-cMyBP-C could be employed as an important clinical tool in patient stratification, early diagnosis in at risk patients before HFpEF, determination of progression, effectiveness of therapeutic approaches, and as a guide in developing future therapies.

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Section: Potential Use Of S-glutathionylated Sarcomere Proteins As Bi...mentioning

confidence: 99%

Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis

Rosas¹,

Solaro

2023

Front. Cardiovasc. Med.

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“…However, new biomarkers of myocardial injury are being increasingly identified. Cardiac myosin-binding protein C is a novel biomarker of myocardial injury that is more sensitive and has the advantage of rising and falling more quickly than cardiac troponin [ 73 ]. This allows for more efficient tracking of the onset and resolution of acute hypertension-mediated organ damage, especially following intervention.…”

Section: Challenges In Evaluation Classifications and Treatment Of Ca...mentioning

confidence: 99%

Cardiac Complications of Hypertensive Emergency: Classification, Diagnosis and Management Challenges

Talle

Ngarande

Doubell

et al. 2022

JCDD

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While mortality in patients with hypertensive emergency has significantly improved over the past decades, the incidence and complications associated with acute hypertension-mediated organ damage have not followed a similar trend. Hypertensive emergency is characterized by an abrupt surge in blood pressure, mostly occurring in people with pre-existing hypertension to result in acute hypertension-mediated organ damage. Acute hypertension-mediated organ damage commonly affects the cardiovascular system, and present as acute heart failure, myocardial infarction, and less commonly, acute aortic syndrome. Elevated cardiac troponin with or without myocardial infarction is one of the major determinants of outcome in hypertensive emergency. Despite being an established entity distinct from myocardial infarction, myocardial injury has not been systematically studied in hypertensive emergency. The current guidelines on the evaluation and management of hypertensive emergencies limit the cardiac troponin assay to patients presenting with features of myocardial ischemia and acute coronary syndrome, resulting in underdiagnosis, especially of atypical myocardial infarction. In this narrative review, we aimed to give an overview of the epidemiology and pathophysiology of hypertensive emergencies, highlight challenges in the evaluation, classification, and treatment of hypertensive emergency, and propose an algorithm for the evaluation and classification of cardiac acute hypertension-mediated organ damage.

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“…Constitutive cMyBP-C phosphorylation, however, improves cardiac function and has cardioprotective effects after ischemic injury 17 . Moreover, upon acute cardiac injury, a cleaved N-terminus of cMyBP-C is released into the bloodstream and was thus shown to be a potential biomarker of a compromised heart 18 – 21 . A recent study found that cMyBP-C phosphorylation might regulate calcium transients and sensitivity via direct contact with tropomyosin to enhance binding between calcium and troponin 22 .…”

Section: Introductionmentioning

confidence: 99%

Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs

et al. 2023

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Skeletal muscle, a highly complex muscle type in the eukaryotic system, is characterized by different muscle subtypes and functions associated with specific myosin isoforms. As a result, skeletal muscle is the target of numerous diseases, including distal arthrogryposes (DAs). Clinically, DAs are a distinct disorder characterized by variation in the presence of contractures in two or more distal limb joints without neurological issues. DAs are inherited, and up to 40% of patients with this condition have mutations in genes that encode sarcomeric protein, including myosin heavy chains, troponins, and tropomyosin, as well as myosin binding protein-C (MYBPC). Our research group and others are actively studying the specific role of MYBPC in skeletal muscles. The MYBPC family of proteins plays a critical role in the contraction of striated muscles. More specifically, three paralogs of the MYBPC gene exist, and these are named after their predominant expression in slow-skeletal, fast-skeletal, and cardiac muscle as sMyBP-C, fMyBP-C, and cMyBP-C, respectively, and encoded by the MYBPC1, MYBPC2, and MYBPC3 genes, respectively. Although the physiology of various types of skeletal muscle diseases is well defined, the molecular mechanism underlying the pathological regulation of DAs remains to be elucidated. In this review article, we aim to highlight recent discoveries involving the role of skeletal muscle-specific sMyBP-C and fMyBP-C as well as their expression profile, localization in the sarcomere, and potential role(s) in regulating muscle contractility. Thus, this review provides an overall summary of MYBPC skeletal paralogs, their potential roles in skeletal muscle function, and future research directions.

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Cardiac myosin-binding protein C as a biomarker of acute myocardial infarction

Cited by 8 publications

References 5 publications

Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis

Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis

Cardiac Complications of Hypertensive Emergency: Classification, Diagnosis and Management Challenges

Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs

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