Activated Protein C Resistance in Patients with Pre-Eclampsia in Lagos, Nigeria

Background: Preeclampsia is reported to complicate 2% - 8% of pregnancies globally and is an important cause of maternal and perinatal morbidity and mortality. The aetiology and pathogenesis are still poorly understood and substantial improvement has not been made in the prediction, prevention and treatment of the disease. Objective: To compare the frequency of activated protein C resistance (APC-R) in patients with pre-eclampsia to that of normotensive pregnant women and to determine the correlation between activated protein ratio (APC-ratio) and the severity of pre-eclampsia. Methodology: A cross-sectional study was carried out in 100 pre-eclamptic patients and 100 normotensive pregnant controls. The APC-ratio was determined using the modified activated partial thromboplastin time. Study participants with APC-ratio of less than 2.0 were defined as having APC-R. Data was analyzed using SPSS version 22.0. Results: Mean APC-ratio was significantly lower in pre-eclamptics (2.89 ± 1.70) compared to normotensive pregnant women (3.57 ± 1.06) (p = 0.0008) and the levels were also higher in mild (2.95 ± 1.15) compared to severe pre-eclamptics (2.62 ± 1.14). The frequency of APC-R was 26% among women with pre-eclampsia compared to 4% among normotensive controls (p = 0.000). Among 100 pre-eclamptic women 7 (21.2%) out of 33 with mild pre–eclampsia had APC-R, while 19 (28.4%) out of 67 with severe pre-eclampsia had APC-R. APC-ratio had a significant negative correlation with mean arterial blood pressure (r = −0.324;p = 0.000) and proteinuria (r = −0.379;p = 0.000) among study participants. Conclusion: The frequency of activated protein c resistance is significantly higher in pre-eclamptics compared to normotensive pregnant women and this is more pronounced in those with severe pre-eclampsia compared with those with mild disease. APC-R may therefore be used as a marker of severity in the disease.

Protein C deficiency with venous and arterial thromboembolic events

Protein C(PC)is a key component of the vitamin K-dependent coagulation pathway.It exerts anticoagulant effects by inactivating factors V and VIII.Acquired or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous thromboembolism.However,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic stroke.This editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.

Cloning and RNA interference analysis of the salivary protein C002 gene in Schizaphis graminum

The full-length c DNA of functionally-unknown salivary protein C002 in Schizaphis graminum was cloned using rapid amplification of c DNA ends（RACE） and designated as Sg C002（Gen Bank accession no. KC977563）. It is 767 bp long and encodes a protein of 190 amino acid residues with a predicted mass of 21.5 k Da and a predicted cleavage site of N-terminal signal peptide between the 24 th and the 25 th residues. Sg C002 is specifically expressed in salivary gland with the highest level at the 2nd instar. Introducing Sg C002-specific 476-si RNA, but not 546-si RNA to aphids through artificial diet significantly suppressed Sg C002 expression. Silencing Sg C002 gene led to lethality of the aphid on wheat plants, but not on pure artificial diet. Our study demonstrated that artificial diet-mediated RNAi can be a useful tool for research on the roles of genes in aphid salivary gland, and also provided new insights into the characteristics of C002 in wheat aphids.

Recurrent thrombotic occlusion of a transjugular intrahepatic portosystemic stent-shunt due to activated protein C resistance

The transjugular intrahepatic portosystemic stent-shunt (TIPS) has successfully been used in the management of refractory variceal bleeding and ascites in patients with portal hypertension. Major drawbacks are the induction of hepatic encephalopathy and shunt dysfunction. We present a 59-year-old woman with alcoholic liver cirrhosis who received a TIPS because of recurrent bleeding from esophageal varices. Stent occlusion occurred 4 mo after placement of the TIPS. Laboratory testing revealed resistance to activated protein C (APC). Combination therapy with low-dose enoxaparin and clopidogrel could not prevent her recurrent stent occlusion. Finally, therapy with high-dose enoxaparin was sufficient to prevent further shunt complications up to now (follow-up period of 1 year). In conclusion, early occlusion of a TIPS warrants testing for thrombophilia. If risk factors are confirmed,anticoagulation should be intensified. There are currently no evidence-based recommendations regarding the best available anticoagulant therapy and surveillance protocol for patients with TIPS.

Protective Effects of Activated Protein C on Neurovascular Unit in a Rat Model of Intrauterine Infection-Induced Neonatal White Matter Injury

Summary： Activated protein C （APC）, a natural anticoagulant, has been reported to exert direct vascu- loprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. In- traperitoneal injection of 300 ~tg/kg lipopolysaccharide （LPS） was administered consecutively to preg- nant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infec- tion-induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats imme- diately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eo- sin （H＆E）. Immunohistochemistry was used to evaluate myelin basic protein （MBP） expression in the periventricular white matter region. Blood-brain barrier （BBB） permeability and brain water content ~were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 （PAR1）. Typical pathological changes of white matter injury were ob- served in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely acti- vated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein ex- pression levels were both down-regulated. Our results suggested that APC exerted neuroprotective ef- fects on multiple components of the neurovascular unit in neonatal rats with intrauterine infec- tion-induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.

Liver myofibroblasts activate protein C and respond to activated protein C

AIM:To study the protein C activation system in human liver myofibroblasts,and the effects of activated protein C(APC)on these cells.METHODS:Human liver myofibroblasts were obtained by outgrowth.Expression of protease activated receptor 1(PAR-1),endothelial protein C receptor(EPCR) and thrombomodulin(TM)was analyzed by flow cytometry.Extracellular signal-regulated kinase(ERK)1/2 activation was assessed by Western blotting using anti-phospho-ERK antibodies.Collagen synthesis was studied with real-time reverse transcription-polymerase chain reaction(RT-PCR).Activation of protein C was studied by incubating liver myofibroblasts with zymogen protein C in the presence of thrombin and detecting the generation of APC with a colorimetric assay using a peptide substrate. RESULTS:Primary cultures of human liver myofibroblasts expressed EPCR on their surface,together with PAR-1 and TM.This receptor system was functional since exposure of myofibroblasts to APC inducedERK1/2 phosphorylation in a dose-and time-dependent manner.Furthermore,APC significantly upregulated the expression of collagen mRNA,as shown by real-time RT-PCR.Collagen upregulation was controlled through the ERK pathway as it was inhibited when using the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor PD98059.Finally,using a cell-based colorimetric assay,we showed that intact myofibroblasts converted protein C into APC in the presence of thrombin.CONCLUSION:These data suggest that APC is a new modulator of liver myofibroblast activity and contributes to the pathophysiology of chronic liver diseases.

Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells

Objective: To investigate the effect of activated protein C (APC) on inflammatory responses in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). Methods: The second passage of collagenase digested HUVEC was divided into the following groups: serum free medium control group (SFM control), phosphate buffer solution control group (PBS control), LPS group with final concentration of 1 μg/ml (LPS group), APC group with final concentration of 7 μg/ml, Pre-APC group (APC pretreatment for 30 min prior to LPS challenge), and Post-APC group (APC administration 30 min after LPS challenge). Supernatant was harvested at 0, 4, 8, 12 and 24 h after LPS challenge. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were analyzed with ELISA. Cells were harvested at 24 h after LPS challenge, and total RNA was extracted. Mes-senger RNA levels for IL-6 and IL-8 were semi-quantitatively determined by RT-PCR. Results: Compared with control group, IL-6 and IL-8 levels steadily increased 4 to 24 h after LPS stimulation. APC treatment could increase LPS-induced IL-6 and IL-8 production. The mRNA levels of IL-6 and IL-8 exhibited a similar change. Conclusion: APC can further increase the level of IL-6 and IL-8 induced by LPS. The effect of these elevated cytokines is still under investigation.

Markers for neural degeneration and regeneration:novel highly sensitive methods for the measurement of thrombin and activated protein C in human cerebrospinal fluid

Inflammation and coagulation are tightly interconnected in the pathophysiology of neuronal diseases.Thrombin,a pro-coagulant serine protease is associated with neurodegeneration and its indirect inhibitor,activated protein C(aPC),is considered neuroprotective.While levels of thrombin and aPC activity are readily measured in the blood,similar assays in the cerebrospinal fluid(CSF)have not been described.The aim of this study was to establish a specific and sensitive enzymatic assay to measure both thrombin and aPC activity in the CSF.CSF was collected from 14 patients with suspected normal pressure hydrocephalus served as a control group,while seven patients with central nervous system infections served as an acute neuro-inflammatory study group and one sample of CSF following traumatic lumbar puncture served as a positive control.Thrombin and aPC activities were measured by fluorescence released by specific proteolytic cleavage in the presence of endopeptidase and amino-peptidase inhibitors to ensure specificity.Specificity of the method was verified by thrombin and serine-protease inhibitors N-alpha-((2-naphthylsulfinyl)glycyl)-DL-p-amidinophenylalanylpiperidine and phenylmethanesulfonyl fluoride.Inhibition of thrombin activity by CSF samples and levels of specific thrombin inhibitors were also assessed.Thrombin and aPC activities were reliably measured and were significantly higher in the CSF of patients with central nervous system infections compared to normal pressure hydrocephalus controls,suggesting the involvement of these factors in neuro-inflammation.CSF thrombin activity levels in the presence of known thrombin concentration were high in patients with central nervous system infections,and low in normal pressure hydrocephalus patients.Quantification of endogenous thrombin inhibitors protease nexin 1,amyloid precursor protein and anti-thrombin III in CSF by western blot indicated a significant elevation of amyloid precursor protein in infectious CSF.In conclusion,this study describes a novel and sensitive assay aimed at the detection of thrombin and aPC activity in CSF.This method may be useful for measuring these factors that reflect degenerative and protective influences of coagulation on neurological disorders.The study procedure was approved by the Ethics Committee of the Chaim Sheba Medical Center(approval No.4245-17-SMC)on October 18,2018.

Resistance to activated protein C is a risk factor for fibrostenosis in Crohn’s disease

AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fi brostenosis in patients with Crohn’s disease (CD). METHODS: In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective case- controlled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR, matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen. RESULTS: The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with f ibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a signifi cantly shorter median time interval from diagnosis of CD to the fi rst operation with fi brostenosis (32 vs 160 mo). At 10 years, the likelihood of remaining free of operation with fi brostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR. CONCLUSION: CD patients with aPCR are at higher risk to undergo intestinal operation of fi brostenosis than those without aPCR. This supports our hypothesis of aPCR being a possible risk factor for fi brostenosis in CD.

Systemic lupus erythematosus combined with primary hyperfibrinolysis and protein C and protein S deficiency:A case report

BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to thrombosis.In contrast,patients with primary hyperfibrino-lysis tend to bleed.CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with"tuberculous pleurisy"and treated with anti-tuberculosis drugs and prednisone.The coagulation-related laboratory results showed decreased fibrinogen,PC activity,PS activity,and antithrombinШactivity.The immune-related laboratory results showed positive antinuclear antibody,anti-Smith antibody,anticardiolipin antibody(ACL),anti-β2-glycoprotein I antibody(aβ2GPI)and direct Coomb’s test and decreased complement 3 and complement 4.Thoracoscopy was performed and bloody pleural fluid was drained.Pathology of the pleural biopsy showed lymphocytes,plasma cells,and a few eosinophils in adipose and fibrous connective tissue.Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases.The patient was finally diagnosed with SLE and primary hyperfibrinolysis,and was treated with prednisolone,hydroxychloroquine,and compound cyclophosphamide.CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI.SLE and primary hyperfibrinolysis can coexist in one patient,with both a risk of thrombosis and a risk of bleeding.

Hyperfibrinogenemia and Reduced Plasma Protein C Levels in HIV-Infected Patients

Background: Heamatological problems have been associated with human immunodeficiency virus infection. Hypercoagulability, in particular, thrombosis is becoming more common in HIV-positive patients. Aim: The goals of this study were to determine levels of plasma fibrinogen, protein C, Hemoglobin, and ESR among Sudanese HIV-positive patients. Materials and Methods: This is a case-control study, for this investigation, a total of 100 participants were recruited for this study. Fifty people were diagnosed with HIV, 25 of whom were males (50 percent) and 25 of whom were females (50 percent), with an average age of 35.5 years. Further fifty healthy people, 26 (52%) of whom were men and 24 (48%) of whom were women, with a mean age of 37.1 years, matched the case group. Fresh Poor Plasma was obtained by centrifuging citrated venous blood samples at 3000 rpm for 15 minutes. The fibrinogen level was determined using an automated coagulation analyzer. Total protein C level was measured by a fully-automated blood coagulation analyzer (SYSMEX CA-500’JAPAN). The haemoglobin parameter was measured from EDTA anticoagulant samples using the Sysmex KX 21-N automated haematological analyzer. In one hour, the ESR was done using a Westergren tube. Data was collected using a structured direct questionnaire. SPSS version 21 was used to analyse the data. Results: The current study discovered that in Sudanese HIV infection, the mean and standard deviation of plasma fibrinogen levels were statistically substantially higher than in the normal control group (370.5 ± 67 vs 214.7 ± 21 with P value 0.001). Protein C levels were statistically significantly lower in HIV positive patients compared with control group (0.6 ± 0.1 vs 1.3 ± 0.2 with P value 0.001). In HIV positive patients, haemoglobin was statistically substantially lower than in healthy people (10.8 ± 1.8 vs 13.7 ± 1.9, P value 0.01). The erythrocyte sedimentation rate was statistically significantly higher in HIV positive patients than in the control group, with (58.00 ± 27 vs 7.68 ± 3 with P value 0.00). Conclusions: HIV infected patients had higher plasma fibrinogen levels and lower haemoglobin levels than normal healthy control groups. In 16 percent of HIV positive patients, protein C deficiency was discovered. HIV-positive patients had significantly greater ESR.

Down Protein C and S Antigen Could Be Predictor of Mortality Outcome in Critical Egyptian COVID-19 Illness

Background: One of the most serious morbidity and mortality features in COVID-19 is thrombo-embolic manifestation with disturbed hemostasis in natural anticoagulant. Protein S plays a critical role in cytokine storming and acts as cross talk between immune status and coagulation process. So, we aimed to address its role in addition to protein C in severity and outcome of disease, with its role in vaccinated people by AstraZeneca. Methods: The present study was conducted on 70 COVID-19 positive by real-time PCR. 40 of patients had moderate symptoms of respiratory, 30 cases were admitted into ICU of Mansoura University Hospital, some of them under mechanical ventilator. In addition to 40 healthy volunteers after first dose of vaccinated AstraZenka as reference, assessment of protein C&S antigen was done by ELIZA. Results: Significant increase in total leucocytic count in COVID-19 than vaccinated volunteer with significant reduction in absolute lymphocytosis, increased neutrophilia. First significant observation was higher MPV in COVID-19 than vaccinated, in addition to significantly higher C-reactive protein in severe cases than moderate and vaccinated. Prominent interesting finding in our study was significant reduction in Protein C&S in severe cases than moderate and vaccinated. Logistic regression analysis revealed that both could be predictor of mortality outcome as CRP in COVID-19 illness. Conclusion: There was significant reduction in protein C&S in severe cases than moderate and vaccinated. Regression analysis shows that could be predictor of mortality as well as CRP, D-dimer. Large extended study and follow up are needed to assess the incidence of thromboembolism and role of protein C&S in different variety protocols of vaccination programs.

The Relationship between Activated Protein C-Resistance and Recurrent Abortion

The activated protein C-resistance (APC-R) method based on APTT was used in 40 nonpregnant multiparas (control group) and 55 patients with abortion of unknown origin (experimental group) in order to explore the relationship between APC-R and recurrent abortion. A significant difference in APC-R-positive rate was found (P<0. 01 ) between control group and experimental group, with the rate being 5 % in the controls and 25. 5 % in the experimental group. And the APC-R-pos- itive rates in the patients with only twice abortions and the patients over-3-time abortions were 22. 6 % and 29. 2 %, respectively (P>0. 05). The APC-R-positive rate, which was 37. 9 % in the patients of late abortion, was much higher than that in the patients of early abortion. It is concluded that APC-R has something to do with recurrent abortion, and is closely related to late abortion, but bears no obvious relationship with times of abortions.

Portal vein thrombosis with protein C-S deficiency in a noncirrhotic patient

There are several conditions that can lead to portal vein thrombosis(PVT), including including infection, malignancies, and coagulation disorders. Anew condition of interest is protein C and S deficiencies, associated with hypercoagulation and recurrent venous thromboembolism. We report the case of a non-cirrhotic 63-year-old male diagnosed with acute superior mesenteric vein thrombosis and PVT and combined deficiencies in proteins C and S, recanalized by short-term low molecular heparin plus oral warfarin therapy.

Myosin binding protein C:Structural abnormalities in familial hypertrophic cardiomyopathy

The muscle protein myosin binding protein C (MyBPC) is a large multi-domain protein whose role in the sarcomere is complex and not yet fully understood. Mutations in MyBPC are strongly associated with the heart disease familial hypertrophic cardiomyopathy (FHC) and these experiments of nature have provided some insight into the intricate workings of this protein in the heart. While some regions of the MyBPC molecule have been assigned a function in the regulation of muscle contraction, the interaction of other regions with various parts of the myosin molecule and the sarcomeric proteins, actin and titin, remain obscure. In additic n, several intra-domain interactions between adjacent MyBPC molecules have been identified. Although the basic structure of the molecule (a series of immunoglobulin and fibronectin domains) has been elucidated, the assembly of MyBPC in the sarcomere is a topic for debate. By analysing the MyBPC sequence with respect to FHC-causing mutations it is possible to identify individual residues or regions of each domain that may be important either for binding or regulation. This review looks at the current literature, in concert with alignments and the structural models of MyBPC, in an attempt to understand how FHC mutations may lead to the disease state.

Activated protein C: A regulator of human skin epidermal keratinocyte function

Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

DETERMINATION OF PROTEIN C, PROTEIN S ANTIGENS AND THEIR CLINICAL SIGNIFICANCE

PC and PS antigens were measured in 370 cases of 12 different diseases and 14 women at third trimester of pregnancy. The PC level was found significantly raised in coronary heart disease, diabetes, nephrotic syndrome, stroke, aplastic anemia and the third trimester of pregnancy, decreased in chronic hepatitis, acute fulminant hepatitis, cirrhosis and deep vein thrombosis (DVT) and no change in acute hepatitis, primary liver carcinoma, Buerger’s disease and leukemia. Total PS was increased in type Ⅱdiabetes, acute lymphocytic leukemia and DVT, and decreased in Berger’s disease, liver diseases, aplastic anemia and the third trimester of pregnancy. In majority of the cases, the total PS and free PS changed parallelly except in Buerger’s disease, DVT and preeclampsia. No correlation was found between PC and PS, PC and AT-Ⅲ.

Down Regulated Protein C Plasma Levels in the Absence of Factor V Leiden Mutation in HIV Patients: An Observational Study in Maiduguri, North-Eastern Nigeria

Background: As life expectancy of HIV-infected patients increases with use of highly active antiretroviral therapy (HAART), protean haematologic manifestation including decreased activity of natural anticoagulants such as protein C may occur in the absence of genetic risk factors. Based on this preposition, we assessed the plasma level of protein C, and prevalence of factor V Leiden mutation among HIV-infected individuals. Our cohort consisted of 499 HIV-infected patients, of which 250 had AIDS, while 249 were either asymptomatic or had minor mucocutaneous infection consistent with WHO clinical stages I and II without features of AIDS. We also evaluated 251 healthy, HIV-negative subjects as controls. All participants were tested for plasma protein C levels and factor V Leiden (FVL) mutation (Arg 506 Gln) by automation and amplification created restriction enzyme site (ACRES) polymerase chain reaction, respectively. The prevalence of reduced protein C plasma levels among HIV positive patients was 20%;it was more prevalent among those that had AIDS compared with those without features of AIDS, but within WHO clinical stage I and II, (93.3% vs 6.7%) respectively. None of the control patients had either reduced protein C nor FVL mutation. All participants that demonstrated reduced protein C plasma levels demonstrated normal FVL genotype (1691G/G). Conclusion: Decreased protein C plasma levels can occur in HIV-infected patients in the absence of factor V Leiden mutation. The risk increases with severity of the disease. Deranged protein C plasma level increases the risk of hypercoagulable state in patients with advanced HIV disease;it should be considered among the causes of thrombo embolism in this group of patients.

Research Progress of Cardiac Myosin Binding Protein C in Dilated Cardiomyopathy and Other Cardiac Conditions

Since its discovery, myosin-binding protein C (cMyBP-C) has become a protein of interest clinically. With emergence of new methodologies and technologies, the structure and functions of cMyBP-C from different aspects can be studied, enabling us to better understand its involvement in certain cardiac conditions. Studying its kinetics of release and clearance from the circulation and by comparing to other conventional biomarkers, it has been reported that cMyBP-C is eligible to be a novel biomarker for several cardiac conditions. Moreover, studying the genetics and their involvement in pathogenic mechanisms has opened the ideas for potential therapeutic strategies. More and more researches are constantly being done to better understand the role of cMyBP-C in dilated cardiomyopathy (DCM). The importance of cMyBP-C to the heart is still actively being investigated. Its presence is however crucial for sarcomere organization and proper regulation of cardiac contraction during systole and complete relaxation during diastole. Genetic mutation in cMyBP-C has been linked to cardiac conditions including hypertrophic and dilated cardiomyopathies. Around 350 types of mutations have already been documented leading to various cardiac conditions and abnormalities. Analyzing human heart samples has enabled us to better understand the importance of cMyBP-C and how its mutations lead to inherited cardiomyopathies. It is therefore necessary to have an update about the research progress of cMyBP-C in relation to DCM and other cardiac conditions.