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At least 19 recordsLinked to original sources
PubMed2026

Novel association of NAV3 with dilated cardiomyopathy and its role in cardiac fibrosis.

A genome-wide association study (GWAS) identified neuron navigator 3 (NAV3) as a potential genetic determinant of myocardial recovery in dilated cardiomyopathy (DCM). This study aimed to understand its functional role in cardiac pathophysiology by leveraging omics approaches. Single-cell RNA-seq transcriptomic data from previously published adult human hearts indicate that NAV3 expression is highest in cardiac fibroblasts, suggesting its functional role in these cells. In vitro, stimulation of primary human ventricular cardiac fibroblasts with transforming growth factor β1 (TGF-β1) induced NAV3 expression in a dose and time-dependent manner. Small-interfering-RNA-mediated knockdown of NAV3 significantly attenuated TGF-β1-induced fibroblast activation, reducing the expression of α-smooth muscle actin (α-SMA), collagens, and fibronectin. RNA sequencing of NAV3-silenced fibroblasts, confirmed by Western blot, revealed upregulation of cell cycle regulators and downregulation of profibrotic markers, suggesting that NAV3 facilitates TGF-β1-induced cell cycle arrest and fibroblast-to-myofibroblast transition. Notably, NAV3 silencing did not alter canonical SMAD2/3 phosphorylation, implying a role for NAV3 in modulating fibrotic signaling through other pathways. Our findings provide functional and mechanistic insights into NAV3's novel role in cardiac fibrosis, showing that reduced NAV3 expression attenuates TGF-β1-mediated fibroblast activation by regulating cell cycle signaling. These results support further investigation of NAV3 as a potential modulator of cardiac fibrosis and myocardial recovery in DCM.NEW & NOTEWORTHY This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.

Humans↗
PubMed1979

Histopathological types of cardiac fibrosis in myocardial disease.

Myocardial fibrosis is a frequently observed pathologic finding. It is a common practice to differentiate macroscopic scarring and microscopic scarring, but there has been little attempt to distinguish the various types of interstitial fibrosis, and to determine their prevalence in different cardiac disorders. In this study, we have semiquantitatively assessed microscopic scarring, interfibre and perivascular fibrosis and a distinctive type of plexiform fibrosis. We examined ten hearts with congestive cardiomyopathy, ten with hypertrophic cardiomyopathy, ten with severe valvular aortic stenosis and ten normal hearts. Perivascular and interfibre fibrosis were quantitatively closely linked and most marked in the congestive cardiomyopathy and the valvular aortic stenosis groups. Plexiform fibrosis occurred maximally in the hypertrophic obstructive cardiomyopathy group, closely associated with myocardium exhibiting muscle fibre disarray. Our study demonstrates that although different types of interstitial fibrosis have particular associations with certain disease entities, the associations are not specific. The recognition of the prevalence of one or more types of interstitial fibrosis may, however, assist in the histopathologic diagnosis of certain myocardial disorders.

Adult↗
PubMed1977

Small cardiac lesions. Fibrosis of papillary muscles and focal cardiac myocytolysis.

Three types of small cardiac lesions were described and illustrated: (1) focal type of papillary muscle fibrosis, evidently a healed infarct of the papillary muscle present in 13% of autopsies, is a histologically characteristic lesion associated with coronary artery disease and healed myocardial infarction, (2) diffuse type of papillary muscle fibrosis, probably an aging change present in almost half of the autopsies, is associated with sclerosis of the arteries in the papillary muscle, is identifiable histologically, and apparently is not associated with any cardiac abnormality, and (3) focal cardiac myocytolysis, a unique histologic lesion, usually multifocal without predilection for any area of the heart, is associated with ischemic heard disease, death due to cancer complicated by nonbacterial thrombotic endocarditis and microthrombi in small cardiac arteries as well as with other diseases. Differentiation of the 2 types of papillary muscle fibrosis is important in the study of papillary muscle and mitral valve dysfunction. Focal cardiac myocytolysis may contribute to the fatal extension of myocardial infarcts.

Aged↗
PubMed2026

Role of semaphorin 4f in cardiac fibroblasts to regulate matrix production through actin remodeling and YAP/TAZ activation.

Cardiac fibrosis remains a critical determinant of adverse outcomes in heart disease, yet effective anti-fibrotic therapies are lacking. While multiple semaphorin family members participate in cardiovascular pathophysiology, the role of semaphorin 4f (Sema4f) in cardiac fibrosis remains unexplored. This study investigates the role and mechanisms of Sema4f in fibrotic remodeling post-myocardial infarction (MI). We employed flow cytometry to characterize cell type-specific Sema4f expression patterns in post-MI hearts. Lineage-specific knockout mice (fibroblast vs. myeloid) were subjected to left anterior descending ligation to assess functional consequences. Proteomic analysis of Sema4f-deficient cardiac fibroblasts was conducted to identify downstream effectors. Key pathways were subsequently validated using pharmacological inhibitors. We found that Sema4f expression was markedly upregulated during the fibrotic phase post-MI, primarily due to fibroblast activation. Fibroblast-, but not myeloid-, specific Sema4f deletion significantly reduced fibrosis and improved cardiac function. Proteomic profiling revealed that Sema4f deficiency led to downregulation of pro-fibrotic gene expression, which was associated with impaired actin cytoskeletal remodeling and decreased nuclear translocation of YAP/TAZ. Pharmacological inhibition of either actin remodeling or YAP/TAZ activity attenuated fibrosis, whereas YAP/TAZ activation abolished the anti-fibrotic effects of Sema4f knockout. Our study provides the first evidence demonstrating the functional role of Sema4f in cardiac fibroblast activation and fibrosis progression. We have identified a fibroblast-specific mechanism mediated by the Sema4f-actin cytoskeleton-YAP/TAZ axis, offering novel mechanistic insights into fibrosis regulation and revealing a promising therapeutic target for cardiac fibrosis with potential clinical applications.

Animals↗
PubMed2026

Artificial intelligence-derived myocardial fibrosis on cardiac magnetic resonance for prognosis in cardiomyopathy: A systematic review of a sparse evidence base.

BACKGROUND: Myocardial fibrosis on cardiovascular magnetic resonance (CMR), assessed by late gadolinium enhancement (LGE) and parametric mapping, is an established predictor of adverse events in cardiomyopathy. We assessed whether artificial intelligence (AI) quantification of fibrosis adds independent prognostic value. METHODS: We searched six databases, a clinical-trials register, and a preprint server from inception to 13 June 2026. Eligible studies used AI to generate a fibrosis marker in adults with ischemic or nonischemic cardiomyopathy, with covariate-adjusted outcomes over ≥12 months. Risk of bias was assessed using PROBAST, PROBAST+AI, and QUIPS. Fewer than three comparable studies precluded meta-analysis; certainty was rated using GRADE. RESULTS: Of 448 records (381 after de-duplication), 18 full texts were reviewed and two included, one peer-reviewed and one preprint. In an ischemic-cardiomyopathy registry (Ghanbari et al.; n = 216 analytic, 26 events), AI-derived dense LGE scar predicted arrhythmic events (univariable hazard ratio [HR] 2.35, 95% CI 1.33-4.15), and AI-derived but not manual scar improved discrimination beyond guideline criteria (area under the curve 0.63 to 0.68; p = 0.02). In a nonischemic dilated-cardiomyopathy preprint (Kim et al.; n = 347, 119 events), automated extracellular volume ≥30% predicted cardiovascular death or heart-failure hospitalization (adjusted HR 2.00, 95% CI 1.32-3.03). Both were at high risk of bias, with data-derived thresholds and no external validation. CONCLUSIONS: Across only two studies, AI-derived fibrosis was independently associated with adverse cardiovascular events, but its added value over manual quantification remains unproven. Certainty was very low. The evidence base is sparse and not yet ready for clinical use.

Humans↗
PubMed1977

Methysergide-induced heart disease: a case of multivalvular and myocardial fibrosis.

Methysergide (Sansert) is known to cause mitral and aortic valvular fibrosis and dysfunction, but has generally not been known to damage right heart valves or the myocardium, and cardiac fibrosis has not been considered to be a risk if therapy is intermittently interrupted. The woman who is the subject of this case report developed catheterization-proven severe tricuspid and moderate aortic and mitral regurgitation during noncontinuous therapy with methysergide. In addition, right ventricular endomyocardial biopsy revealed extensive endocardial and intramyocardial fibrosis.

Aortic Valve Insufficiency↗
PubMed1976

Endocardial changes produced in Patus monkeys by the ablation of cardiac lymphatics and the administration of a plantain diet.

The effect of obliteration of the cardiac lymph drainage and prolonged feeding with a plantain diet in Patus monkeys was studied. Althout obliteration of the cardiac lymph supply produced fibroelastotic lesions the addition of a plantain diet did not usually produce much increase in cardiac fibrosis and the changes of EMF or CUO were not seen. The reasons for this are discussed.

Animals↗
PubMed2024

A novel mouse model recapitulates the effects of rs2254524 variant in the lanosterol synthase gene on salt sensitivity and organ damage.

OBJECTIVE: The blood pressure (BP) response to salt intake (salt sensitivity) shows great variability among individuals and is more frequent in hypertensive patients. Elevated levels of the steroid hormone Endogenous Ouabain (EO) are associated with hypertension (HT) and salt sensitivity. The lanosterol synthase gene ( LSS ) plays a key role in the biosynthesis of steroids and its rs2254524 variant (Val642Leu) is linked to salt sensitivity in humans. This study aims to investigate the pathophysiological significance of the Lss missense variation in a new knock-in mouse model of salt-sensitive HT onset. METHODS: We generated a mouse model carrying the murine homolog (Val643Leu) of the human LSS variant. C57BL/6N LssV643L/V643L mice were fed different NaCl diets (low-salt, LSD; normal-salt, NSD; high-salt, HSD) and were characterized at functional, histological, and molecular levels. RESULTS: At baseline, mutant mice showed an enlarged kidney compared to the wild-type (WT) counterpart, but the Lss V643L variant did not affect EO biosynthesis nor systolic BP at 3 and 12 months. In HSD, we observed an increased systolic BP only in 12-month-old LssV643L/V643L mice, compared to NSD. Moreover, only the HSD LssV643L/V643L mice showed cardiac hypertrophy and a higher incidence of cardiac fibrosis compared to WT at 12 months. Finally, the Lss mRNA level was differentially regulated by HSD in the adrenal gland, liver, and heart of LssV643L/V643L mice compared to WT. CONCLUSIONS: The novel Lss mouse model resembles the salt-sensitive HT phenotype observed in hypertensive patients and provides a good model of salt-sensitive HT and HT-mediated organ damage.

Animals↗
PubMed2026

A Fibroblast-Based Adenoviral Reporter System Driven by the Mouse Collagen Type I Alpha 1 Promoter for Antifibrotic Drug Screening.

Cardiac fibrosis, characterized by aberrant fibroblast activation and excessive extracellular matrix deposition, lacks target-specific therapies, largely due to the absence of longitudinal, scalable, and non-destructive in vitro screening platforms. Traditional end-point assays and resource-intensive stem cell models inherently preclude real-time monitoring of fibrotic progression. To overcome these limitations, this protocol describes the generation, optimization, and validation of a mouse collagen type I alpha 1 (Col1a1) promoter-driven adenoviral mCherry fluorescent reporter system (Ad-mCol1a1p-mCherry) in NIH/3T3 fibroblasts. The critical steps for recombinant adenovirus packaging, transduction optimization (multiplicity of infection) to minimize cytotoxicity, and the establishment of a robust transforming growth factor beta (TGF-β)-induced fibrosis model are detailed. By circumventing the need for cell fixation, this system enables direct and longitudinal monitoring of collagen transcription in live cells. The model's specificity and reliability are pharmacologically validated using the TGF‑β type I receptor (ALK5) inhibitor SB431542, with fluorescent readouts correlating with endogenous fibrotic markers quantified via reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Ultimately, this cost-effective platform provides an accessible tool for the high-throughput screening of novel antifibrotic agents, thereby accelerating translational cardiovascular research.

Animals↗
PubMed1979

Noninvasive evaluation of ventricular function in cystic fibrosis.

The cardiac function of 21 patients with cystic fibrosis was studied using radionuclides and M-mode echocardiography. The patients (mean age 13.2 years, range 4 to 27) had a wide range of clinical and pulmonary function abnormalities (mean Shwachman-Kulczycki score 62.1). Decreased right ventricular ejection fraction was found in 13 of 18 patients (72%); an additional four patients had abnormal septal motion on ECHO. Left ventricular ejection fraction was abnormal at rest in four patients (19%); an additional four patients had borderline low LVEF. The LV pre-ejection period to ejection time ratio increased significantly (i.e., worsening LV performance) with deterioration of S-K score, chest radiograph score, and forced expiratory volume in 1 second. Three of eight patients with normal LVEF at rest had an abnormal response to supine bicycle exercise: LVEF fell in two patients and was unchanged in one. Thus evidence of LV dysfunction was observed in seven of 21 (33%) of the patients; four at rest and in three only during exercise.

Adolescent↗
PubMed1979

Echocardiographic profiles of the long-term cardiac changes in cystic fibrosis.

In this echocardiographic study, assessment of the heart in children with cystic fibrosis has shown that changes occur in not only the right ventricle but also in the left ventricle and aorta, as compared with normal. Echocardiograms could be successfully performed in 34 of 37 patients. The thickness of the right ventricular anterior wall and the dimension of the right ventricular cavity were abnormal, even in patients with mild disease (National Institutes of Health [NIH] score for severity of disease of 85 or greater). Larger, older children with lower NIH score had disproportionately larger right ventricular anterior walls and cavities. The thickness of the septal wall, the thickness of the left ventricular posterior wall, and the aortic dimensions were increased in those with severe disease. The dimensions of the left ventricular cavity for the population were slightly but significantly smaller than normal in systole and in diastole throughout the course of the disease. This study demonstrates that echocardiography is an effective noninvasive means of assessing the long-term changes in children with cystic fibrosis. These changes occur in both sides of the heart and appear to worsen as the disease progresses.

Adolescent↗
PubMed1976

Myocardial necrosis, fibrosis, and DNA synthesis in experimental cardiac hypertrophy induced by sudden pressure overload.

The development of myocardial fibrosis as a result of cardiac hypertrophy was studied in 11 cats in which the pulmonary artery was banded, six rabbits in which the ascending aorta was banded, and eight cats with various congenital cardiac anomalies. Histological examination of the myocardium revealed multifocal areas of degeneration and necrosis with healing by fibrosis in the right ventricle of cats in which the pulmonary artery was banded and in the left ventricle of rabbits in which the aorta was banded. In five of eight cats with congenital anomalies, myocardial necrosis and fibrosis were not present in spite of heart weight to body weight ratios 2-4 times greater than in the experimental models. In the other three cats, fibrosis was subendocardial or diffuse rather than multifocal as in the banded animals. This suggests that the increased connective tissue found in animals with cardiac hypertrophy induced by banding the aorta or pulmonary artery is an artifact of the preparation. Autoradiographic studies of the myocardium of pulmonary artery-banded cats indicated that all newly synthesized DNA in this model is restricted to interstitial cell and endothelial cell proliferation.

Animals↗
PubMed1975

Amyloid in the aged heart: frequency and clinical significance.

Cardiac amyloid accumulation is a common autopsy finding in elderly persons, the frequency increasing with each advancing age decade. In most cases the deposits are microscopic, confined to the atrial subendocardium, and of dubious significance. In a few cases, however, there is much more extensive cardiac involvement, with infiltration of the ventricular musculature and intracardiac conduction system. In the authors' recent autopsy study of 100 patients over 60 years of age, 10 had diffuse cardiac amyloidosis with biventricular involvement. Microscopically, the amyloid deposits often resembled foci of interstitial fibrosis. Significant cardiac enlargement (weight greater than 380 gm) was present in only 2 of these patients, and in only one of them were the clinical signs and symptoms clearly attributable attributable to the amyloid infiltration. It was difficult to assess the possible contribution of ventricular amyloid to congestive failure since most of the patients also had coronary arteriosclerosis. In the aged, clinically significant cardiac amyloidosis associated with cardiac enlargement appears to be part of a disease spectrum more commonly characterized by focal, clinically insignificant cardiac amyloid deposits. Yet several features suggest that senile cardiac amyloidosis may differ from the clinically significant cardiac amyloidosis occassionally seen in younger patients.

Aged↗
PubMed2026

Non-telomeric function deficiency of TERT enhances pressure overload-induced mouse cardiac remodeling by activation of CNBP-mediated THBS3/ITGB1 pathway.

Recent studies show that telomerase reverse transcriptase (TERT) possesses important new biological functions in gene transcription regulation, signal transduction, tumorigenesis, vascular development and mitochondrial DNA protection independent of the maintenance of telomere length. In this study we investigated the role and mechanisms of TERT in regulating the gene expression and signal transduction during pressure overload-induced cardiac remodeling. The first-generation TERT knockout (Tert-/-) and wild-type littermate control (Tert+/+) male mice were subjected to transverse aortic constriction (TAC) surgery to establish a pressure overload-induced cardiac remodeling model. We showed that pressure overload significantly increased TERT expression in the hearts at 8 weeks after TAC, whereas TERT deficiency remarkably exacerbated pressure overload-induced cardiac dysfunction, cardiac hypertrophy and fibrosis, and reduced the survival rate of the mice. In contrast, TERT overexpression reversed phenylephrine (PE)-stimulated cardiomyocyte hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Ttranscriptomic and proteomic analyses revealed that extracellular matrix (ECM)-receptor interaction was a key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway regulated by TERT in hemodynamic overload-induced cardiac remodeling. TERT knockdown greatly enhanced, while TERT overexpression inhibited the activation of the THBS3/ITGB1 signaling pathway, in which transcription factor cellular nucleic acid-binding protein (CNBP) played a pivotal mediating role by interacting with TERT. In conclusion, the non-telomeric function of TERT in gene transcription regulation and signaling transduction plays an important role during pressure overload-induced myocardial remodeling via modulating CNBP-mediated THBS3/ITGB1 signaling pathway, which provides new targets and strategies for the prevention and treatment of pressure overload-induced cardiac remodeling.

Animals↗
PubMed1979

Autoantibodies and the spectrum of Sjögren's syndrome.

In studies reported recently, the sera of patients with Sjögren's syndrome were found to contain precipitating antibodies to nuclear antigens that can be identified by immunodiffusion analysis. These precipitating autoantibodies have been termed SS-A and SS-B antibodies. We show that identification of these autoantibodies helped in establishing the diagnosis of Sjögren's syndrome in 12 of 30 patients in whom the diagnosis had not been considered at the time of the physician's initial examination. The reasons for this were related to lack of spontaneous complaints of keratoconjunctivitis sicca and xerostomia and prominence of symptoms associated with arthritis, myalgia, pulmonary fibrosis, and cardiac disease. This study re-emphasizes the importance of multisystem disease in Sjögren's syndrome and shows that specific serologic assays for autoantibodies aided in diagnosis.

Aged↗
PubMed1976

A clinicopathological study on the electrical axis of the heart in 1,000 autopsy cases.

The electrical axis of the heart in 1,000 aged people more than 56 years of age was classified as normal axis in 58%, left axis deviation in 17.4%, mild left axis devaition in 21.9%, and right axis deviation in 2.7%. Pathological examination disclosed that left axis deviation was associated with myocardial infarction in 20%, right bundle branch block in 16%, but showed no significant relationships with coronary sclerosis, myocardial fibrosis and cardiac hypertrophy. Right axis deviation was associated with right bundle branch block in 66.7% and right ventricular hypertrophy in 22.2%

Aged↗
PubMed1979

Nutritional properties of poppyseed oil relative to some other oils.

Male Wistar rats were fed a purified basal diet with 20% lard and corn oil (3:1), sunflower oil, poppyseed oil, low-erucic rapeseed oil from Brassica napus, cultivar Tower, or mixtures of these oils, for 1 or 26 weeks. None of the hearts exhibited lipidosis at 1 week. At 26 weeks, the level of serum triglycerides was higher in rats fed the mixture of lard and corn oil than in those fed only vegetable oil, and the incidence of cardiac necrosis and fibrosis was higher in rats fed the rapeseed oil than in the other animals. Cardiac phospholipids in rats fed the rapeseed oil contained an elevated level of omega 3 docosahexaenoic acid, particularly in phosphatidylethanolamine. Poppyseed oil exhibited properties similar to those of sunflower oil, was absorbed as well as olive oil, and appeared to be a promising oil for human consumption.

Animals↗
PubMed1978

Effect of selenium-vitamin E on adriamycin-induced cardiomyopathy in rabbits.

Administration of selenium-vitamin E (Se-E) to weanling rabbits chronically treated with adriamycin (ADR) resulted in decreased incidence and severity of cardiomyopathy and decreased cumulative mortality during a 10-week experiment. However, Se-E did not protect against extracardiac lesions or against a number of clinicopathologic alterations induced by chronic ADR toxicosis. Histopathologic alterations of ADR-induced cardiomyopathy were concentrated periarterially in the free and septal walls of the left ventricle. Initial vacuolar degeneration of injured cardiac muscle cells was followed by myofibrillar lysis and eventual cell death with subsequent interstitial fibrosis. Ultrastructurally, degenerated cardiac muscle cells had 3 prominent alterations: (1) sarcoplasmic vacuolization caused by distention of elements of sarcoplasmic reticulum and T-tubules, (2) degeneration of mitochondria forming large myelin figures from disrupted membranes, and (3) lysis of myofibrils producing granular sarcoplasmic masses. Severely injured fibers were necrotic and macrophages invaded to remove cellular debris. The interstitium was distended by edema and increased amounts of collagen. Extracardiac lesions in rabbits with chronic ADR toxicosis included the usually recognized alterations involving cell-renewal systems in kidney, testis, bone marrow, skin, and alimentary tract, as well as vacuolar degeneration of skeletal muscle and focal loss of pancreatic tissue, with ensuing pancreatic fibrosis and fat necrosis. Deaths in ADR-treated rabbits usually were precipitated by terminal septic embolism. The partial protection afforded by Se-E against ADR-induced cardiomyopathy may be associated with stabilization of the membranes of injured muscle cells or with prevention of ADR-induced inhibition of coenzyme Q10-dependent mitochondrial enzymes.

Alopecia↗