Short term Pm2.5 exposure caused a robust lung inflammation, vascular remodeling, and exacerbated transition from left ventricular failure to right ventricular hypertrophy.
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ABSTRACT:
SUBMITTER: Yue W
PROVIDER: S-EPMC6411784 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:Left ventricular (LV) hypertrophy, a marker for adverse cardiovascular events, is more common in blacks than in non-Hispanic whites. Mechanisms leading to LV hypertrophy and mediating its clinical sequelae in blacks are not fully understood. We investigated the associations of 39 candidate biomarkers in distinct biological pathways with LV mass and geometry in blacks. Participants included 1193 blacks (63±9 years of age; 72% women; 78% hypertensive) belonging to hypertensive sibships. LV mass was measured by transthoracic echocardiography and indexed to height.(2.7) LV geometry was categorized as normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Generalized estimating equations were used to assess associations of the 39 biomarkers with LV mass index after adjustment for age, sex, and conventional risk factors. After adjustment for potential confounders, log-transformed levels of the following biomarkers were independently associated with LV mass index: N-terminal pro-brain natriuretic peptide (?±SE=0.07±0.01 pg/mL; P<0.0001), mid-regional pro-atrial natriuretic peptide (?±SE=0.08±0.02 pmol/L; P<0.0001), mid-regional pro-adrenomedullin (?±SE=0.09±0.03 nmol/L; P=0.0006), C-terminal pro-endothelin (?± SE=0.05±0.02 pmol/L; P=0.0009), and osteoprotegerin (?±SE=0.07±0.02 pg/mL; P=0.0005) (? is for 1 log increase in biomarker level). The associations of these biomarkers with LV mass index were mainly due to their association with eccentric hypertrophy. Higher circulating levels of natriuretic peptides, adrenomedullin, endothelin, and osteoprotegerin were associated with increased LV mass index, providing insights into the pathophysiology of LV hypertrophy in blacks.
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Project description:BackgroundPerforation of the interventricular septum and left ventricular (LV) free wall by a right ventricular (RV) lead is an extremely rare and potentially life-threatening complication. In this case report, we discussed the diagnosis and management of a very unusual complication of pacemaker (PM) implantation, i.e., LV perforation brought on by an RV pacing lead.Case summaryA 92-year-old man was admitted to Xiangyang No.1 People's Hospital due to a complete atrioventricular block. We performed a dual-chamber PM implantation; however, on the second postoperative day (POD), pacemaker failure occurred. Thoracic computed tomography (CT) scan showed that RV lead had pierced the interventricular septum and LV free wall. A transvenous lead extraction of the penetrating lead was performed uneventfully, and RV lead was refixed at the lower RV septum on the 5th POD.DiscussionIdentification of high-risk patients is mandatory to prevent this serious complication, and transvenous lead extraction with cardiac surgery backup may be an option.
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Project description:BACKGROUND:Although sex differences in heart failure (HF) prevalence and severity have been recognized, its molecular mechanisms are poorly understood. We used a tachycardia-induced cardiomyopathy model to determine the sex specific remodeling pattern in male and female adult pigs. METHODS:We compared the echocardiographic and molecular measures of myocardial remodeling in 19 male and 12 female pigs with chronic symptomatic systolic HF due to right ventricle (RV) pacing (170 bpm) and 6 male and 5 female sham-operated controls. Males achieved subsequent HF stages earlier than females. RESULTS:The progression of symptomatic HF was associated with the reduction of the left ventricle (LV) ejection fraction in both sexes (all p?<?0.05). A significant LV dilatation occurred only in males (p?<?0.001). The HF development was accompanied by an increased pro-hypertrophic factor GATA4 and TGF-?1 messenger RNA (mRNA) expression in the LV only in male pigs (all p?<?0.01). The total gelatinolytic activity in LV was higher in males than females (irrespective of HF, p?<?0.05), and the HF progression was associated with a reduced total gelatinolytic activity (p?<?0.05) in the LV only in males. No differences in LV myocardial collagen content were found between HF groups and sexes. Cardiomyocyte cross-sectional diameter was significantly smaller in male hearts as compared to female (p?<?0.05). CONCLUSIONS:Male and female porcine hearts respond differently to RV pacing. Males, most likely due to a higher extracellular matrix turnover, demonstrated a significant LV dilatation, followed by a strong induction of pro-hypertrophic program, and an earlier development of symptomatic HF.
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Project description:We reported the RNAseq analyses of right ventricle (RV) and left ventricle (LV) in neonatal volume overload (VO) and sham-operated SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV and LV free wall of P7 from VO and sham-operated rat. It demonstrated that the 1806 differentially expressed genes (DEGs) between RV and LV at the neonatal stage were primarily enriched in GTPase mediating signal transduction, insulin signaling pathway and thyroid hormone signaling pathway. VO produced 3 more times DEGs in LV than RV . GO analysis of these DEGs demonstrated that in the top 150 enriched terms, the LV comparison and RV comparison shared 34 terms (22.7%) in common. These commonly enriched terms were primarily associated with GTPase mediating signal transduction. KEGG analysis of these DEGs demonstrated that in the top 30 enriched terms, the LV comparison and RV comparison shared 14 terms (46.7%) in common. And insulin signaling pathway and thyroid hormone signaling pathway are the top two enriched terms in common. Regarding the differently enriched GO terms, they were primarily associated with lipid metabolism and ion channel in RV and primarily associated nucleic acid metabolism in LV. The top two differently enriched KEGG terms were arrhythmogenic right ventricular cardiomyopathy (ARVC) and adipocytokine signaling pathway in RV while microRNAs in cancer and longevity regulating pathway in LV. These results were further confirmed by the determination of metabolites.
2022-12-15 | GSE186247 | GEO
Project description:MicroRNAs (miRs) are small, noncoding RNAs that are emerging as crucial regulators of cardiac remodeling in left ventricular hypertrophy (LVH) and failure (LVF). However, there are no data on their role in right ventricular hypertrophy (RVH) and failure (RVF). This is a critical question given that the RV is uniquely at risk in patients with congenital right-sided obstructive lesions and in those with systemic RVs. We have developed a murine model of RVH and RVF using pulmonary artery constriction (PAC). miR microarray analysis of RV from PAC vs. control demonstrates altered miR expression with gene targets associated with cardiomyocyte survival and growth during hypertrophy (miR 199a-3p) and reactivation of the fetal gene program during heart failure (miR-208b). The transition from hypertrophy to heart failure is characterized by apoptosis and fibrosis (miRs-34, 21, 1). Most are similar to LVH/LVF. However, there are several key differences between RV and LV: four miRs (34a, 28, 148a, and 93) were upregulated in RVH/RVF that are downregulated or unchanged in LVH/LVF. Furthermore, there is a corresponding downregulation of their putative target genes involving cell survival, proliferation, metabolism, extracellular matrix turnover, and impaired proteosomal function. The current study demonstrates, for the first time, alterations in miRs during the process of RV remodeling and the gene regulatory pathways leading to RVH and RVF. Many of these alterations are similar to those in the afterload-stressed LV. miRs differentially regulated between the RV and LV may contribute to the RVs increased susceptibility to heart failure.
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Project description:Studies have demonstrated that increased oxidative stress contributes to the pathogenesis and the development of pulmonary artery hypertension (PAH). Extracellular superoxide dismutase (SOD3) is essential for removing extracellular superoxide anions, and it is highly expressed in lung tissue. However, it is not clear whether endogenous SOD3 can influence the development of PAH. Here we examined the effect of SOD3 knockout on hypoxia-induced PAH in mice and a loss-of-function SOD3 gene mutation (SOD3(E124D)) on monocrotaline (40 mg/kg)-induced PAH in rats. SOD3 knockout significantly exacerbated 2 weeks of hypoxia-induced right ventricular (RV) pressure and RV hypertrophy, whereas RV pressure in SOD3 knockout mice under normoxic conditions is similar to wild-type controls. In untreated control rats at age of 8 weeks, there was no significant difference between wild-type and SOD3(E124D) rats in RV pressure and the ratio of RV weight:left ventricular weight (0.25±0.02 in wild-type rats versus 0.25±0.01 in SOD3(E124D) rats). However, monocrotaline caused significantly greater increases of RV pressure in SOD3(E124D) rats (48.6±1.8 mm Hg in wild-type versus 57.5±3.1 mm Hg in SOD3(E124D) rats), of the ratio of RV weight:left ventricular weight (0.41±0.01 versus 0.50±0.09; P<0.05), and of the percentage of fully muscularized small arterioles in SOD3(E124D) rats (55.2±2.3% versus 69.9±2.6%; P<0.05). Together, these findings indicate that the endogenous SOD3 has no role in the development of PAH under control conditions but plays an important role in protecting the lung from the development of PAH under stress conditions.
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Project description:Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.
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Project description:Mechanisms of right ventricular (RV) dysfunction in heart failure (HF) are poorly understood. RV response to volume overload (VO), a common contributing factor to HF, is rarely studied. The goal was to identify interventricular differences in response to chronic VO. Rats underwent aorto-caval fistula (ACF)/sham operation to induce VO. After 24 weeks, RV and left ventricular (LV) functions, gene expression and proteomics were studied. ACF led to biventricular dilatation, systolic dysfunction and hypertrophy affecting relatively more RV. Increased RV afterload contributed to larger RV stroke work increment compared to LV. Both ACF ventricles displayed upregulation of genes of myocardial stress and metabolism. Most proteins reacted to VO in a similar direction in both ventricles, yet the expression changes were more pronounced in RV (pslope: < 0.001). The most upregulated were extracellular matrix (POSTN, NRAP, TGM2, CKAP4), cell adhesion (NCAM, NRAP, XIRP2) and cytoskeletal proteins (FHL1, CSRP3) and enzymes of carbohydrate (PKM) or norepinephrine (MAOA) metabolism. Downregulated were MYH6 and FAO enzymes. Therefore, when exposed to identical VO, both ventricles display similar upregulation of stress and metabolic markers. Relatively larger response of ACF RV compared to the LV may be caused by concomitant pulmonary hypertension. No evidence supports RV chamber-specific regulation of protein expression in response to VO.
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Project description:Left ventricular (LV) hypertrophy is a strong independent predictor of increased cardiovascular morbidity and mortality in clinical and population-based samples. Clinical and hemodynamic stimuli to LV hypertrophy induce not only an increase in cardiac mass and wall thickness but also a fundamental reconfiguration of the protein, cellular and molecular components of the myocardium. Several studies have indicated that LV mass is influenced by genetic factors. The substantial heritability (h(2)) for LV mass in population-based samples of varying ethnicity indicates robust genetic influences on LV hypertrophy. Genome-wide linkage and association studies in diverse populations have been performed to identify genes influencing LV mass, and although several chromosomal regions have been found to be significantly associated with LV mass, the specific genes and functional variants contained in these chromosomal regions have yet to be identified. In addition, multiple studies have tried to link single-nucleotide polymorphisms (SNPs) in regulatory and pathway genes with common forms of LV hypertrophy, but there is little evidence that these genetic variations are functional. Up to this point in time, the results obtained in genetic studies are of limited clinical value. Much of the heritability remains unexplained, the identity of the underlying gene pathways, genes, and functional variants remains unknown, and the promise of genetically-based risk prediction and personalized medicine remain unfulfilled. However, molecular biological technologies continue to improve rapidly, and the long-term potential of sophisticated genetic investigations using these modern genomic technologies, coupled with smart study designs, remains intact. Ultimately, genetic investigations offer much promise for future prevention, early intervention and treatment of this major public health issue.
| S-EPMC3499934 | biostudies-literature
Project description:Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR.Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ? 13 mm and >1.5-fold the thickness of the opposing myocardial segment.Ninety-one patients (61 ± 21 years; 57 male) with aortic stenosis (aortic valve area 0.93 ± 0.32 cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17 ± 2mm) with hypertrophic cardiomyopathy.We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common.
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