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Journal of the American College of... Aug 2023Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness.
BACKGROUND
Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness.
OBJECTIVES
This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses.
METHODS
RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis.
RESULTS
RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm accompanied by interstitial and perivascular fibrosis.
CONCLUSIONS
RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.
Topics: Humans; Myocytes, Cardiac; Hypertension, Pulmonary; Atrial Fibrillation; Heart Atria; Atrial Appendage
PubMed: 37587582
DOI: 10.1016/j.jacc.2023.05.063 -
American Journal of Translational... 2024Heart failure poses a significant threat to global public health within the realm of cardiovascular diseases. Its pathological progression involves various alterations... (Review)
Review
Heart failure poses a significant threat to global public health within the realm of cardiovascular diseases. Its pathological progression involves various alterations in cardiomyocytes, among which autophagy, a crucial intracellular degradation mechanism, plays a pivotal role. Autophagy facilitates the breakdown of damaged organelles and proteins, thereby maintaining cellular homeostasis. In the context of heart failure, autophagy coexists with apoptosis and necrosis, influencing myocardial hypertrophy and ventricular remodeling. However, its impact on heart failure manifests a dual nature: moderate autophagy aids in cardiac repair, whereas excessive autophagy may exacerbate ventricular remodeling and cell demise. This review delves into the fundamental biology of autophagy, elucidating its involvement in the pathological cascade of heart failure and its correlation with cardiac hypertrophy and ventricular remodeling. Furthermore, an analysis of the interplay between autophagy regulatory factors and heart failure sheds light on the potential therapeutic implications of autophagy in the prevention and management of heart failure. This exploration provides a theoretical foundation for novel treatment strategies in combating heart failure.
PubMed: 38883358
DOI: 10.62347/OBXQ9477 -
Arquivos Brasileiros de Cardiologia 2023Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass,...
BACKGROUND
Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events.
OBJECTIVE
To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients.
METHODS
A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests.
RESULTS
A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg.
CONCLUSION
High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.
Topics: Humans; Blood Pressure Monitoring, Ambulatory; Hypertrophy, Left Ventricular; Cross-Sectional Studies; Hypertension; Blood Pressure; Obesity
PubMed: 37820172
DOI: 10.36660/abc.20230050 -
Cardiovascular Diabetology Jul 2023L-type Ca channel Ca1.2 is essential for cardiomyocyte excitation, contraction and gene transcription in the heart, and abnormal functions of cardiac Ca1.2 channels are...
BACKGROUND
L-type Ca channel Ca1.2 is essential for cardiomyocyte excitation, contraction and gene transcription in the heart, and abnormal functions of cardiac Ca1.2 channels are presented in diabetic cardiomyopathy. However, the underlying mechanisms are largely unclear. The functions of Ca1.2 channels are subtly modulated by splicing factor-mediated alternative splicing (AS), but whether and how Ca1.2 channels are alternatively spliced in diabetic heart remains unknown.
METHODS
Diabetic rat models were established by using high-fat diet in combination with low dose streptozotocin. Cardiac function and morphology were assessed by echocardiography and HE staining, respectively. Isolated neonatal rat ventricular myocytes (NRVMs) were used as a cell-based model. Cardiac Ca1.2 channel functions were measured by whole-cell patch clamp, and intracellular Ca concentration was monitored by using Fluo-4 AM.
RESULTS
We find that diabetic rats develop diastolic dysfunction and cardiac hypertrophy accompanied by an increased Ca1.2 channel with alternative exon 9* (Ca1.2), but unchanged that with alternative exon 8/8a or exon 33. The splicing factor Rbfox2 expression is also increased in diabetic heart, presumably because of dominate-negative (DN) isoform. Unexpectedly, high glucose cannot induce the aberrant expressions of Ca1.2 exon 9* and Rbfox2. But glycated serum (GS), the mimic of advanced glycation end-products (AGEs), upregulates Ca1.2 channels proportion and downregulates Rbfox2 expression in NRVMs. By whole-cell patch clamp, we find GS application hyperpolarizes the current-voltage curve and window currents of cardiac Ca1.2 channels. Moreover, GS treatment raises K-triggered intracellular Ca concentration ([Ca]), enlarges cell surface area of NRVMs and induces hypertrophic genes transcription. Consistently, siRNA-mediated knockdown of Rbfox2 in NRVMs upregulates Ca1.2 channel, shifts Ca1.2 window currents to hyperpolarization, increases [Ca] and induces cardiomyocyte hypertrophy.
CONCLUSIONS
AGEs, not glucose, dysregulates Rbfox2 which thereby increases Ca1.2 channels and hyperpolarizes channel window currents. These make the channels open at greater negative potentials and lead to increased [Ca] in cardiomyocytes, and finally induce cardiomyocyte hypertrophy in diabetes. Our work elucidates the underlying mechanisms for Ca1.2 channel regulation in diabetic heart, and targeting Rbfox2 to reset the aberrantly spliced Ca1.2 channel might be a promising therapeutic approach in diabetes-induced cardiac hypertrophy.
Topics: Animals; Rats; Calcium; Calcium Channels, L-Type; Cardiomegaly; Diabetes Mellitus, Experimental; Glycation End Products, Advanced; Myocytes, Cardiac; RNA Splicing Factors
PubMed: 37415128
DOI: 10.1186/s12933-023-01894-5 -
The Journal of General Physiology Jul 2023Connexin-43 (Cx43) is the most abundant protein forming gap junction channels (GJCs) in cardiac ventricles. In multiple cardiac pathologies, including hypertrophy and...
Connexin-43 (Cx43) is the most abundant protein forming gap junction channels (GJCs) in cardiac ventricles. In multiple cardiac pathologies, including hypertrophy and heart failure, Cx43 is found remodeled at the lateral side of the intercalated discs of ventricular cardiomyocytes. Remodeling of Cx43 has been long linked to spontaneous ventricular arrhythmia, yet the mechanisms by which arrhythmias develop are still debated. Using a model of dystrophic cardiomyopathy, we previously showed that remodeled Cx43 function as aberrant hemichannels (non-forming GJCs) that alter cardiomyocyte excitability and, consequently, promote arrhythmias. Here, we aim to evaluate if opening of remodeled Cx43 can serve as a general mechanism to alter cardiac excitability independent of cellular dysfunction associated with a particular cardiomyopathy. To address this issue, we used a genetically modified Cx43 knock-in mouse (S3A) that promotes cardiac remodeling of Cx43 protein without apparent cardiac dysfunction. Importantly, when S3A mice were subjected to cardiac stress using the β-adrenergic agonist isoproterenol (Iso), they displayed acute and severe arrhythmias, which were not observed in WT mice. Pretreatment of S3A mice with the Cx43 hemichannel blocker, Gap19, prevented Iso-induced abnormal electrocardiographic behavior. At the cellular level, when compared with WT, Iso-treated S3A cardiomyocytes showed increased membrane permeability, greater plasma membrane depolarization, and Ca2+ overload, which likely caused prolonged action potentials, delayed after depolarizations, and triggered activity. All these cellular dysfunctions were also prevented by Cx43 hemichannel blockers. Our results support the notion that opening of remodeled Cx43 hemichannels, regardless of the type of cardiomyopathy, is sufficient to mediate cardiac-stress-induced arrhythmogenicity.
Topics: Mice; Animals; Connexin 43; Myocardium; Myocytes, Cardiac; Arrhythmias, Cardiac; Gap Junctions; Ion Channels; Cardiomyopathies; Isoproterenol
PubMed: 37191672
DOI: 10.1085/jgp.202213150 -
Vascular Health and Risk Management 2023Hypertension is one of the main preventable cardiovascular (CV) risk factors all over the years, closely related to CV morbidity and mortality. One of the most common... (Review)
Review
Hypertension is one of the main preventable cardiovascular (CV) risk factors all over the years, closely related to CV morbidity and mortality. One of the most common hypertensive target organ damages is hypertensive heart disease (HHD), including left ventricular hypertrophy, which progresses gradually and leads to systolic or diastolic dysfunction of the left ventricular, and finally to end-stage heart failure. Regarding its prevalence and the need for early diagnosis, assessment of heart imaging examination is of major importance. Echocardiography has been used as the standard imaging technique to evaluate HHD for years, providing an accurate evaluation of the left ventricular geometry, along with the systolic and diastolic function. However, nowadays there is a growing interest in cardiovascular magnetic resonance (CMR). Despite the importance of the use of echocardiography in everyday clinical practice, numerous studies have shown the superiority of CMR as an imaging technique for clinical and research purposes, mainly due to its strength to provide an unlimited area of view, as well as the identification and quantification of the type and extent of myocardial fibrosis. Hence, this review aims to analyze the importance of heart imaging in the hypertensive population, with a special interest in CMR imaging.
Topics: Humans; Heart Diseases; Hypertrophy, Left Ventricular; Hypertension; Cardiomyopathies; Magnetic Resonance Imaging
PubMed: 38045022
DOI: 10.2147/VHRM.S436133 -
Journal of Ethnopharmacology Jan 2024Dohongsammul-tang (DH) is a Korean traditional herbal medicine used to alleviate symptoms caused by extravasated blood. It is known to protect against cardiovascular...
ETHNOPHARMACOLOGICAL RELEVANCE
Dohongsammul-tang (DH) is a Korean traditional herbal medicine used to alleviate symptoms caused by extravasated blood. It is known to protect against cardiovascular diseases and promote blood circulation by activating blood circulation to dispel blood stasis. The DH based on the characteristics of its medicinal properties has discovered the potential of alleviating cardiac hypertrophy. Therefore, this study was performed to verify the pharmacological effect of DH on improving cardiovascular disorders and to demonstrate its mutual improvement effect on renal function. Furthermore, aim of this study is founding the new potential beyond the traditional medicinal efficacy of DH, a traditional medicine.
AIM OF THE STUDY
In cardiovascular disease, cardiac hypertrophy refers to a change in the shape of the heart's structure due to pressure overload. It is known that an increase in myofibrils causes thickening of the heart, resulting in high blood pressure. Therefore, suppressing cardiac hypertrophy may be a major factor in lowering the morbidity, mortality, and heart failure associated with cardiovascular disease. Therefore, the study was performed to investigate whether DH, traditionally used, has effects on improving and alleviating cardiac injury and fibrosis caused by cardiac hypertrophy.
MATERIALS AND METHODS
Dohongsamul-tang was composed of 6 herbal medicine and each material were boiled with 4 L distilled water for 2 h. The mixture for dohongsamul-tang centrifuged at 3000 rpm for 10 min and concentrated. The concentrated dohongsamul-tang extraction freeze-dried and sotred at 70 °C. The powder of dohongsamul-tang was diluted with distilled water and administered orally. In this study, pressure overload was induced by tying the transverse aortic arch, which is connected to the left ventricle, to the thickness of a 27G needle by performing a surgical operation. The resulting cardiac hypertrophy and heart remodeling was induced and maintained for 8 weeks.
RESULTS
The study administered propranolol and dohongsamul-tang orally for 10 weeks to investigate their effects on cardiac hypertrophy induced by transverse aortic contraction (TAC) surgery. Results showed that TAC group increased the left ventricle weight and decreased cardiac function, but dohongsamul-tang treatment attenuated these effects. The pressure-volume curve experiment revealed that dohongsamul-tang improved cardiovascular function, which was worsened by TAC group. Dohongsamul-tang treatment also downregulated collagen I and III through the TGF-β/Smad2 signaling pathway and improved hematological biomarkers of cardiac hypertrophy. In addition, dohongsamul-tang treatment improved renal function-related biomarkers, such as blood creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin, which were increased by TAC-induced cardiac hypertrophy.
CONCLUSIONS
Taken together, dohongsamul-tang treatment inhibited cardiac remodeling due to pressure overload in the TAC-induced cardiac hypertrophy model, and this effect is thought to be manifested by improving the functional and morphological changes through the calcineurin/NFATc4 and reducing the cardiac fibrosis by suppressing TGF-β/Smad2 signaling pathways.
Topics: Animals; Mice; Calcineurin; Cardiovascular Diseases; Ventricular Remodeling; Cardiomegaly; Fibrosis; Transforming Growth Factor beta; Plant Extracts; Water; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37453625
DOI: 10.1016/j.jep.2023.116844 -
International Journal of Sports Medicine May 2024Changes in cardiac geometry develop after intense and prolonged training. Left ventricular enlargement, increased relative wall thickness, and growing mass of the left...
Changes in cardiac geometry develop after intense and prolonged training. Left ventricular enlargement, increased relative wall thickness, and growing mass of the left ventricle occur after strenuous exercise. Combat sports such as judo can lead to left ventricular hypertrophy. Previous studies have found that there are differences in left ventricular chamber size and thickness between the sexes, with female athletes having smaller wall diameters and less hypertrophy than male athletes. The research aims to examine heart muscle adaptations and remodeling of cardiac geometry among elite judo athletes and to evaluate differences between males and females. A cross-sectional study included a group of 19 (males n=10, females n=9) professional judokas between 20 and 30 years. Demographic and anthropometric data were collected. Cardiac geometry was determined by two-dimensional transthoracic echocardiography. In terms of left ventricular mass and the left ventricular mass index significant differences were found between male and female judokas (233.44±68.75 g vs. 164.11±16.59 g, p=0.009), (105.16±24.89 vs. 84.66±15.06, p=0.044), respectively. A greater enlargement of the heart muscle is observed in male athletes compared to the female group. Left ventricle enlargement is likely to occur among elite-level judokas.
Topics: Humans; Martial Arts; Female; Male; Cross-Sectional Studies; Hypertrophy, Left Ventricular; Echocardiography; Adult; Sex Factors; Young Adult; Heart Ventricles; Athletes; Ventricular Remodeling; Adaptation, Physiological
PubMed: 38401535
DOI: 10.1055/a-2252-1239 -
Trends in Cardiovascular Medicine May 2024Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils, mainly derived from transthyretin, either wild-type or... (Review)
Review
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils, mainly derived from transthyretin, either wild-type or hereditary variants, or immunoglobulin light chains misfolding. It is characterized by an increased left ventricular (LV) mass and diastolic dysfunction, which can lead to heart failure with preserved ejection fraction and/or conduction disturbances. The diagnosis is based on invasive pathology demonstration of amyloid deposits, or non-invasive criteria using advanced cardiovascular imaging techniques. Nevertheless, 12-lead electrocardiogram (ECG) remains of crucial importance in the assessment of patients with CA, since they can manifest peculiar features such as low QRS voltages, in discordance with the LV hypertrophy, but also pseudo-infarction patterns, sinus node dysfunction, atrioventricular blocks, premature supraventricular and ventricular beats, which support the presence of a myocardial disease. Great awareness of these common ECG characteristics of CA is needed to increase diagnostic performance and improve patient's outcome. In the present review, we discuss the current role of the ECG in the diagnosis and management of CA, focusing on the most common ECG abnormalities and rhythm disorders.
Topics: Humans; Electrocardiography; Cardiomyopathies; Arrhythmias, Cardiac; Predictive Value of Tests; Amyloidosis; Heart Rate; Prognosis; Action Potentials; Ventricular Function, Left; Heart Conduction System
PubMed: 36841466
DOI: 10.1016/j.tcm.2023.02.006 -
JACC. Basic To Translational Science Sep 2023Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy is often characterized by left ventricular hypertrophy,...
Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy is often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation of neuregulin-1β signaling in the heart is a known contributor to heart failure. The systemically administered recombinant human neuregulin-1β for 10 days in our 5/6 nephrectomy-induced model of chronic kidney disease alleviated the progression of uremic cardiomyopathy and kidney dysfunction in type 4 cardiorenal syndrome. The currently presented positive preclinical data warrant clinical studies to confirm the beneficial effects of recombinant human neuregulin-1β in patients with chronic kidney disease.
PubMed: 37791301
DOI: 10.1016/j.jacbts.2023.03.003