Search Results (18)

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion. Full article

Background: Cardiac involvement is a major cause of morbidity and mortality in systemic sclerosis (SSc). Autoantibodies may help identify patients at increased cardiovascular (CV) risk. This systematic review aimed to assess the predictive value of classical and emerging SSc-related autoantibodies for cardiac involvement and their integration with imaging and cardiac biomarkers. Methods: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library up to 16 July 2025. Studies were included if they reported associations between specific autoantibodies and cardiac outcomes (e.g., myocardial fibrosis, conduction abnormalities, arrhythmias, ventricular dysfunction) in adult patients with SSc. Data extraction and quality assessment followed PRISMA 2020 guidelines. The review protocol was registered in PROSPERO (registration ID: CRD420251107782). Results: Anti-topoisomerase I antibodies were associated with myocardial fibrosis, subclinical systolic and diastolic dysfunction, elevated cardiac biomarkers, and pathological findings on cardiac magnetic resonance imaging. Anti-centromere antibodies were linked to conduction system abnormalities, particularly among older individuals. Anti-RNA polymerase III and anti-U3 ribonucleoprotein antibodies correlated strongly with arrhythmias and pericardial involvement. Novel autoantibodies, such as anti-heart antibodies and anti-intercalated disk antibodies, were linked to early myocardial injury, although their clinical utility requires further validation. Across studies, serological markers alone were insufficient to predict cardiac outcomes without concurrent imaging or biomarker evaluation. Conclusions: Autoantibody profiling plays an important role in CV risk stratification in SSc. Combining serological testing with cardiac biomarkers and advanced imaging enhances early detection and supports individualized monitoring. Further longitudinal studies are needed to validate predictive models and optimize patient outcomes. Full article

Background: Autoantibodies against Desmoglein-2 desmosomal protein (anti-DSG2-ab) were identified in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) by Enzyme-Linked ImmunoSorbent Assay (ELISA); anti-intercalated disk autoantibodies (AIDAs) were identified in myocarditis and (ARVC) by indirect immunofluorescence (IFL). We aim to assess: (1) anti-DSG2-ab specificity in ARVC and myocarditis, (2) accuracy of anti-DSG2-ab detection by ELISA versus AIDA by IFL, and (3) clinical correlates of anti-DSG2-ab in ARVC. Methods: We included 77 patients with ARVC, 91 with myocarditis/dilated cardiomyopathy (DCM), 27 with systemic immune-mediated diseases, and 50 controls. Anti-heart antibodies (AHAs) and AIDAs were assessed by IFL, and anti-DSG2-ab by ELISA (assessed both by optical density, OD, and U/L). Receiving operator curve (ROC) analysis was used to assess ELISA diagnostic accuracy. Results: A relevant proportion (56%) of ARVC patients was anti-DSG2-ab-positive, with higher anti-DSG2-ab levels than controls. Anti-DSG2-ab titer was not different between ARVC and myocarditis/DCM patients (48% anti-DSG-ab positive). Frequency of anti-DSG2 positivity by ELISA was higher in AIDA-positive cases by IFL than AIDA-negative cases (p = 0.039 for OD, p = 0.023 for U/L). In ARVC, AIDA-positive patients were more likely to be AHA-positive (p < 0.001), had pre-syncope (p = 0.025), and abnormalities in cardiac rhythm (p = 0.03) than ARVC AIDA-negative patients, while anti-DSG2-ab positivity did not have clinical correlates. Conclusions: Anti-DG2-ab detection in ARVC and myocarditis/DCM reflects immune-mediated pathogenesis to desmosomal proteins. Higher frequency of anti-DSG2-ab positivity by ELISA by U/L was higher in AIDA-positive cases by IFL than AIDA-negative cases, in keeping with the hypothesis that DSG2 is one of AIDA autoantigens. In ARVC, AIDA status but not anti-DSG2-ab showed distinct clinical correlates, possibly reflecting a wider AIDA autoantigenic spectrum. Full article

Edible films based on biopolymers are used to protect food from adverse environmental factors. However, their ample use may be hindered by some challenges to their mechanical and antimicrobial properties. Despite this, in most cases, increasing their mechanical properties and antibacterial activity remains a relevant challenge. To solve this problem, a possible option is to fill the biopolymer matrix of films with a functional filler that combines high reinforcing and antibacterial properties. In this work, biocomposite films based on a mixture of chitosan and cassava starch were filled with a hybrid filler in the form of bentonite clay particles loaded with ginger essential oil (GEO) in their structure with varied concentrations. For this purpose, GEO components were intercalated into bentonite clay interlayer space using a mechanical capture approach without using surface-active and toxic agents. The structure and loading efficiency of the essential oil in the obtained hybrid filler were analyzed by lyophilization and laser analysis of dispersions, ATR-FTIR spectroscopy, thermogravimetry, and X-ray diffraction analysis. The filled biocomposite films were analyzed using ATR-FTIR spectroscopy, optical and scanning electron spectroscopy, energy dispersive spectroscopy, mechanical analysis under tension, and the disk diffusion method for antibacterial activity. The results demonstrated that the tensile strength, Young’s modulus, elongation at the break, and the antibacterial effect of the films increased by 40%, 19%, 44%, and 23%, respectively, compared to unfilled film when the filler concentration was 0.5–1 wt.%. Full article

In this work, passive cooling systems for the revamping of existent silicon photovoltaic (PV) cells were developed and analysed in order to mitigate the efficiency loss caused by temperature rise in the hot season. For this purpose, expanded graphite (EG) was used to stabilize a phase change material (PCM) with a melting temperature close to 53 °C in order to realize thermal management systems (TMSs) able to store heat at constant temperature during melting and releasing it in crystallization. In particular, stearic and palmitic acid mixture (PA-SA) was shape-stabilized in EG at different concentrations (10, 12 and 14 part per hundred ratio) under vacuum into a rotary evaporation apparatus followed by cold compaction; PA-SA leakage was reduced due to its intercalation between the graphite lamellae, and the thermal conductivity necessary to maximize the heat transfer to a bulk TMS was improved via powder cold compaction, which minimizes voids and creates preferential thermal conductive patterns. The composite materials, stable till 150 °C, were tested by differential scanning calorimetry (DSC) at 1 °C/min to precisely determine the phase transition temperatures and the enthalpic content, which was only slightly reduced from 196 J/g of the neat PCM to 169 J/g due to the very low EG fraction necessary for the stabilization. Despite only the 14:100 EG-to-PA-SA ratio, the system’s thermal conductivity was enhanced 40 times with respect to the neat PCM (from 0.2 to 8.3 W/(m K), value never reached in works present in the literature), with a good convergence of the values evaluated through hot disk tests and laser flash analysis (LFA), finding correlation with both graphitic content and density. In order to completely avoid leaking with the consequent dispersion of PCM in the environment during the final application, all the samples were encapsulated in a PE-made film. The mechanical properties were evaluated with compression tests at 30 °C and 80 °C simulating a possible compressive stress deriving from the contact needed to maintain the TMS position on the rear of the PV cells. Finally, the material response was simulated by imposing thermal cycles into a climatic chamber and reproducing the three hottest and coldest days of summer 2022 of two Italian locations, Verona (Veneto, 45° N, 11° E) and Gela (Sicily, 37° N, 14° E), thus highlighting the thermal management effects with delays in temperature increase and daily peak temperature smoothing. The role of EG is strategic for the processing and the properties of the resulting composites in order to realize a proper compromise between the melting enthalpy of PCM and the thermal conductivity enhancement given by EG. Full article

Desmoglein-2 mutations are detected in 5–10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2^mt/wt) or haploinsufficient (Dsg2^0/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2^mt/wt and Dsg2^0/wt mice and in young Dsg2^mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg2^0/wt and Dsg2^mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2^mt/wt mice but not in wild types. Dsg2^mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2^mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2^mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients. Full article

While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function. Full article

The intercalated disk is a cardiac specific structure composed of three main protein complexes—adherens junctions, desmosomes, and gap junctions—that work in concert to provide mechanical stability and electrical synchronization to the heart. Each substructure is regulated through a variety of mechanisms including proteolysis. Calpain proteases, a class of cysteine proteases dependent on calcium for activation, have recently emerged as important regulators of individual intercalated disk components. In this review, we will examine how calcium homeostasis regulates normal calpain function. We will also explore how calpains modulate gap junctions, desmosomes, and adherens junctions activity by targeting specific proteins, and describe the molecular mechanisms of how calpain dysregulation leads to structural and signaling defects within the heart. We will then examine how changes in calpain activity affects cardiomyocytes, and how such changes underlie various heart diseases. Full article

In severe cases of sepsis, endotoxin-induced cardiomyopathy can cause major damage to the heart. This study was designed to see if Vitamin C (Vit C) could prevent lipopolysaccharide-induced heart damage. Eighteen Sprague Dawley male rats (n = 6) were divided into three groups. Rats received 0.5 mL saline by oral gavage in addition to a standard diet (Control group), rats received one dose of endotoxin on day 15 (lipopolysaccharide) (LPS) (6 mg/kg), which produced endotoxemia (Endotoxin group), and rats that received 500 mg/Kg BW of Vit C by oral gavage for 15 days before LPS administration (Endotoxin plus Vit C group). In all groups, blood and tissue samples were collected on day 15, six hours after LPS administration, for histopathological and biochemical analysis. The LPS injection lowered superoxide dismutase (SOD) levels and increased malondialdehyde in tissues compared with a control group. Furthermore, the endotoxin group showed elevated inflammatory biomarkers, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Both light and electron microscopy showed that the endotoxic-treated group’s cardiomyocytes, intercalated disks, mitochondria, and endothelial cells were damaged. In endotoxemic rats, Vit C pretreatment significantly reduced MDA levels and restored SOD activity, minimized biomarkers of inflammation, and mitigated cardiomyocyte damage. In conclusion: Vit C protects against endotoxin-induced cardiomyopathy by inhibiting oxidative stress cytokines. Full article

Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts of AHA and AIDA in SSc. Methods: The study included consecutive SSc patients (n = 116, aged 53 ± 13 years, 83.6% females, median disease duration 7 years) with clinically suspected heart involvement (symptoms, abnormal ECG, abnormal troponin I or natriuretic peptides, and abnormal echocardiography). All SSc patients underwent CMR. Serum AHA and AIDA were measured by indirect immunofluorescence in SSc and in control groups of non-inflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141), and normal blood donors (NBD) (n = 270). AHA and AIDA status in SSc was correlated with baseline clinical, diagnostic features, and outcome. Results: The frequency of AHA was higher in SSc (57/116, 49%, p < 0.00001) than in NICD (2/160, 1%), IHF (2/141, 1%), or NBD (7/270, 2.5%). The frequency of AIDA was higher (65/116, 56%, p < 0.00001) in SSc than in NICD (6/160, 3.75%), IHF (3/141, 2%), or NBD (1/270, 0.37%). AHAs were associated with interstitial lung disease (p = 0.04), history of chest pain (p = 0.026), abnormal troponin (p = 0.006), AIDA (p = 0.000), and current immunosuppression (p = 0.01). AHAs were associated with death (p = 0.02) and overall cardiac events during follow-up (p = 0.017). Conclusions: The high frequencies of AHA and AIDA suggest a high burden of underdiagnosed autoimmune HInv in SSc. In keeping with the negative prognostic impact of HInv in SSc, AHAs were associated with dismal prognosis. Full article

Background: Sarcoidosis is an immune-mediated disease. Cardiac involvement, a granulomatous form of myocarditis, is under-recognized and prognostically relevant. Anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in nonsarcoidosis myocarditis forms. Objective: The aim was to assess serum AHAs and AIDAs as autoimmune markers in cardiac sarcoidosis. Methods: This is a cross-sectional study on AHA and AIDA frequency in: 29 patients (aged 46 ± 12, 20 male) with biopsy-proven extracardiac sarcoidosis and biopsy-proven or clinically suspected and confirmed by 18-fluorodeoxyglucose positron emission tomography and/or cardiovascular magnetic resonance (CMR) cardiac involvement; 30 patients (aged 44 ± 11, 12 male) with biopsy-proven extracardiac sarcoidosis without cardiac involvement (no cardiac symptoms, normal 12-lead electrocardiogram, echocardiography and CMR), and control patients with noninflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141) and normal blood donors (NBDs) (n = 270). Sarcoidosis patients were recruited in two recruiting tertiary centers in the USA and Italy. AHAs and AIDAs were detected by indirect immunofluorescence on the human myocardium and skeletal muscle. Results: AHA and AIDA frequencies were higher in sarcoidosis with cardiac involvement (86%; 62%) than in sarcoidosis without cardiac involvement (0%; 0%), NICD (8%; 4%), IHF (7%; 2%) and NBD (9%; 0%) (p = 0.0001; p = 0.0001, respectively). Sensitivity and specificity for cardiac sarcoidosis were 86% and 92% for positive AHAs and 62% and 98% for positive AIDAs, respectively. AIDAs in cardiac sarcoidosis were associated with a higher number of involved organs (p = 0.04). Conclusions: Serum AHAs and AIDAs provide novel noninvasive diagnostic autoimmune markers for cardiac sarcoidosis. Full article

Aldosterone plays a major role in atrial structural and electrical remodeling, in particular through Ca²⁺-transient perturbations and shortening of the action potential. The Ca²⁺-activated non-selective cation channel Transient Receptor Potential Melastatin 4 (TRPM4) participates in atrial action potential. The aim of our study was to elucidate the interactions between aldosterone and TRPM4 in atrial remodeling and arrhythmias susceptibility. Hyperaldosteronemia, combined with a high salt diet, was induced in mice by subcutaneously implanted osmotic pumps during 4 weeks, delivering aldosterone or physiological serum for control animals. The experiments were conducted in wild type animals (Trpm4^+/+) as well as Trpm4 knock-out animals (Trpm4^-/-). The atrial diameter measured by echocardiography was higher in Trpm4^-/- compared to Trpm4^+/+ animals, and hyperaldosteronemia-salt produced a dilatation in both groups. Action potentials duration and triggered arrhythmias were measured using intracellular microelectrodes on the isolated left atrium. Hyperaldosteronemia-salt prolong action potential in Trpm4^-/- mice but had no effect on Trpm4^+/+ mice. In the control group (no aldosterone-salt treatment), no triggered arrythmias were recorded in Trpm4^+/+ mice, but a high level was detected in Trpm4^-/- mice. Hyperaldosteronemia-salt enhanced the occurrence of arrhythmias (early as well as delayed-afterdepolarization) in Trpm4^+/+ mice but decreased it in Trpm4^-/- animals. Atrial connexin43 immunolabelling indicated their disorganization at the intercalated disks and a redistribution at the lateral side induced by hyperaldosteronemia-salt but also by Trpm4 disruption. In addition, hyperaldosteronemia-salt produced pronounced atrial endothelial thickening in both groups. Altogether, our results indicated that hyperaldosteronemia-salt and TRPM4 participate in atrial electrical and structural remodeling. It appears that TRPM4 is involved in aldosterone-induced atrial action potential shortening. In addition, TRPM4 may promote aldosterone-induced atrial arrhythmias, however, the underlying mechanisms remain to be explored. Full article

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium. Full article

Dental implants are one of the most commonly used ways to replace missing teeth. Nevertheless, the close contact with hard and soft oral tissues expose these devices to infectious peri-implant diseases. To prevent such infection, several surface treatments have been developed in the last few years to improve the antimicrobial properties of titanium dental implants. In this in-vitro pilot study, the antimicrobial activity of titanium surfaces coated with different types of graphene nanoplatelets are investigated. Six different colloidal suspensions of graphene nanoplatelets (GNPs) were produced from graphite intercalated compounds, setting the temperature and duration of the thermal shock and varying the number of the exfoliation cycles. Titanium disks with sand-blasted and acid-etched surfaces were sprayed with 2 mL of colloidal GNPs suspensions. The size of the GNPs and the percentage of titanium disk surfaces coated by GNPs were evaluated through a field emission-scanning electron microscope. The antibacterial activity of the specimens against Staphylococcus aureus was estimated using a crystal violet assay. The dimension of GNPs decreased progressively after each sonication cycle. The two best mean percentages of titanium disk surfaces coated by GNPs were GNPs_1050°/2 and GNPs_1150°/2. The reduction of biofilm development was 14.4% in GNPs_1150°/2, 20.1% in GNPs_1150°/3, 30.3% in GNPs_1050°/3, and 39.2% in GNPs_1050°/2. The results of the study suggested that the surface treatment of titanium disks with GNPs represents a promising solution to improve the antibacterial activity of titanium implants. Full article

Background: Mutations in genes encoding intercalated disk/desmosome proteins, such as plakophilin 2 (PKP2), cause arrhythmogenic cardiomyopathy (ACM). Desmosomes are responsible for myocyte–myocyte attachment and maintaining mechanical integrity of the myocardium. Methods: We knocked down Pkp2 in HL-1 mouse atrial cardiomyocytes (HL-1^Pkp2-shRNA) and characterized their biomechanical properties. Gene expression was analyzed by RNA-Sequencing, microarray, and qPCR. Immunofluorescence was used to detect changes in cytoskeleton and focal adhesion. Antagomirs were used to knock down expression of selected microRNA (miR) in the rescue experiments. Results: Knockdown of Pkp2 was associated with decreased cardiomyocyte stiffness and work of detachment, and increased plasticity index. Altered mechanical properties were associated with impaired actin cytoskeleton in HL-1^Pkp2-shRNA cells. Analysis of differentially expressed genes identified focal adhesion and actin cytoskeleton amongst the most dysregulated pathways, and miR200 family (a, b, and 429) as the most upregulated miRs in HL-1^Pkp2-shRNA cells. Knockdown of miR-200b but not miR-200a, miR-429, by sequence-specific shRNAs partially rescued integrin-α1 (Itga1) levels, actin organization, cell adhesion (on collagen), and stiffness. Conclusions: PKP2 deficiency alters cardiomyocytes adhesion through a mechanism that involves upregulation of miR-200b and suppression of Itga1 expression. These findings provide new insights into the molecular basis of altered mechanosensing in ACM. Full article