Leptin Attenuates Cardiac Hypertrophy in Patients with Generalized Lipodystrophy

Author(s):  
My-Le Nguyen ◽  
Vandana Sachdev ◽  
Thomas R Burklow ◽  
Wen Li ◽  
Megan Startzell ◽  
...  

Abstract Context Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized, GLD) or only some (partial, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia. Objective Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy. Design/Participants/Intervention/Setting Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N=27), and 3-5y (N=23) of metreleptin. Outcome Echocardiograms, blood pressure (BP), triglycerides, A1c, HOMA-IR Results In GLD, metreleptin lowered triglycerides (median(IQR) 740(403-1239), 138(88-196), 211(136-558) mg/dL at baseline, 1y, 3-5y, P<0.0001), A1c (9.5±3.0, 6.5±1.6, 6.5±1.9%, P<0.001), and HOMA-IR (34.1(15.2-43.5), 8.7(2.4-16.0), 8.9(2.1-16.4), P<0.001). Only HOMA-IR improved in PLD (P<0.01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8±1.7, 9.1±1.3, 8.3±1.7 mm, P<0.01), and LV mass (140.7±45.9, 128.7±37.9, 110.9±29.1 g, P<0.01), and increased septal e’ velocity (8.6±1.7, 10.0±2.1, 10.7±2.4 cm/s, P<0.01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e’ velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD. Conclusion Metreleptin attenuated cardiac hypertrophy and improved septal e’ velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A315-A316
Author(s):  
My-Le Nguyen ◽  
Vandana Sachdev ◽  
Thomas Burklow ◽  
Wen Li ◽  
Rebecca J Brown

Abstract Lipodystrophy (LD) syndromes are rare disorders of deficient adipose tissue and severe metabolic disease, including insulin resistance, diabetes, and hypertriglyceridemia. LD may affect all adipose depots (generalized LD, GLD) or only some depots (partial LD, PLD). Low adipose mass leads to very low leptin in GLD, and variable leptin in PL. Treatment with exogenous leptin (metreleptin) improves metabolic disease in LD, particularly GLD. Left ventricular (LV) hypertrophy is frequent in LD, especially GLD. The mechanism for hypertrophy in LD is not known and may relate to glucose or lipotoxicity. We hypothesized that metreleptin would improve cardiac abnormalities in LD, and that this would be mediated by improvements in glucose and triglycerides (TG). We analyzed echocardiograms (echo), blood pressure (BP), heart rate (HR), and metabolic parameters in 38 subjects with LD (18 GLD, 20 PLD) who were treated with metreleptin in open-label clinical studies at the National Institutes of Health. 27 had repeat echo after 1y of metreleptin (mean 1.0 ± 0.2y), and 23 after 3 to 5y (mean 3.7±0.6y). In GLD, metreleptin significantly improved metabolic disease, including reduced TG (median(IQR) 740(403–1239), 138(88–196), 211(136–558) mg/dL at baseline, 1y, & 3-5y, P<0.0001), hemoglobin A1c (9.5±3.0, 6.5±1.6, 6.5±1.9% at baseline, 1y, & 3-5y, P<0.001), and insulin resistance by HOMA-IR (34.1 (15.2–43.5), 8.7 (2.4–16.0), 8.9 (2.1–16.4), P<0.001). Only HOMA-IR improved in PLD (P<0.01). Systolic BP and HR decreased after metreleptin in GLD (BP 120±11, 117±10, 109±16 mmHg, P=0.046; HR 89±9, 82±12, 80±16 bpm, P=0.018; at baseline, 1y, 3-5y, respectively) but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8±1.7, 9.1±1.3, 8.3±1.7 at baseline, 1y, & 3-5y, P<0.01), LV mass (140.7±45.9, 128.7±37.9, 110.9±29.1 at baseline, 1y, & 3-5y, P<0.01), and LV mass index (88.6±22.0, 81.6±16.9, 81.6±16.9 at baseline, 1y, & 3-5y, P<0.01). Metreleptin also improved septal e’ velocity, a measure of early diastolic cardiac function, in GLD (8.6±1.7, 10.0±2.1, 10.7±2.4 at baseline, 1y, & 3-5y, P<0.01). All changes remained significant after adjustment for BP. In GLD, multivariate variable selection models suggested that changes in posterior wall thickness and LV mass index related to metreleptin-induced reductions in TG, and changes in septal e’ velocity related to metreleptin-induced reductions in hemoglobin A1c. No changes in echo parameters were seen in PLD. These findings suggest that metreleptin improves cardiac hypertrophy and diastolic function in patients with GLD, and these improvements may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to a broader, leptin-sufficient population with LV hypertrophy and/or diabetic cardiomyopathy remains to be determined.


2016 ◽  
Vol 45 (4) ◽  
pp. 171
Author(s):  
Ria Nova ◽  
Bambang Madiyono ◽  
Sudigdo Sastroasmoro ◽  
Damayanti R Sjarif

Background Obesity causes cardiovascular disturbances. Theincidence of cardiovascular disease is higher even in mildly obesepatients than in lean subjects.Objectives The purpose of this study was to compare left ven-tricular (LV) mass, LV internal dimensions, and LV systolic func-tion between obese and normal children; and to determine the as-sociation of the degree of obesity with LV mass and LV systolicfunction.Methods This cross-sectional study was conducted on elemen-tary school students in Jakarta from February to April 2003. Wemeasured the subjects’ body weight and height, and performedlipid profile and echocardiography examinations. Measurementsof LV mass, LV internal dimensions with regard to septum thick-ness, LV internal diameter, and LV posterior wall thickness; andLV systolic function as indicated by shortening fraction and ejec-tion fraction, were performed echocardiographically. The differ-ences in measurements between obese and normal children aswell as between obese children with and without lipid abnormalitywere analyzed. The correlation between the degree of obesity withLV size and systolic function was determined.Results Twenty-eight normal children and 62 obese children wereenrolled in the study. Mean LV mass was 35.7 (SD 5.16) g/cm 3 inobese children versus 24.0 (SD 3.80) g/cm 3 in normal children(P<0.0001). Mean septum thickness was 0.8 (SD 0.14) mm inobese children versus 0.6 (SD 7.90) mm in normal children (P<0.0001). Mean posterior wall thickness was 0.9 (SD 0.14) mm inobese children versus 0.6 (SD 9.97) mm in normal children(P<0.0001). Mean LV internal diameter was 4.0 (SD 0.34) mm inobese children versus 3.9 (SD 0.29) mm in normal children(P=0.300). There was strong correlation between the degree ofobesity and LV mass (r=0.838, P<0.0001). LV systolic function(shortening fraction) was 37.1 (SD 4.20) percent in obese childrenversus 35.8 (SD 4.99) percent in normal children (P=0.19). Ejec-tion fraction was 67.4 (SD 5.32) percent in obese children versus65.5 (SD 6.29) percent in normal children (P=0.13). There wasweak correlation between LV systolic function and the degree ofobesity (shortening fraction r=0.219, P=0.038; ejection fractionr=0.239, P=0.023).Conclusions Obese children had significantly greater LV mass,septum thickness, and posterior wall thickness than normal chil-Backgrounddren. Such significant difference was absent for LV internal diam-eter and measures of LV systolic function. There was no signifi-cant difference in LV mass and LV systolic function between obesechildren with or without abnormality of lipid profile. A strong corre-lation exists between the degree of obesity and LV mass, but thecorrelation between degree of obesity and LV systolic function wasweak


2019 ◽  
Vol 37 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Miao Zhang ◽  
Qigen Du ◽  
Fubiao Yang ◽  
Ying Guo ◽  
Yunlong Hou ◽  
...  

Objectives: To investigate the effect of acupuncture at PC6 on cardiac hypertrophy in isoproterenol (ISO)-treated mice. Methods: 48 male C57BL/6 mice underwent subcutaneous injection of ISO for 14 days and were randomly divided into four groups (n=12 each) that remained untreated (ISO group), received verum manual acupuncture (MA) treatment at PC6 (ISO+MA(PC6) group), sham MA at location on the tail not corresponding to any traditional acupuncture point (ISO+MA(tail) group), or propranolol (ISO+PR group). An additional 12 mice were given an injection of phosphate-buffered saline (PBS) and formed a healthy control (Normal) group. After performing echocardiography and measuring the ratio of heart weight (HW)/tibia length (TL) at 14 days, all mice were euthanased. Morphological examination was performed following haematoxylin and eosin and Masson’s staining of heart tissues. Ultrastructural changes were observed by electron microscopy. Cardiac protein expression of atrial natriuretic peptide (ANP) and tumour necrosis factor α (TNFα) were measured by immunohistochemical (IHC) staining and Western blotting. Results: Compared with the untreated model group, acupuncture at PC6 lowered the heart rate, reduced the ratio of HW/TL, improved the left ventricular (LV) anterior wall thickness (LVAWd), LV end-diastolic anterior wall thickness (LVAWs), LV end-systolic posterior wall thickness (LVPWd), LV end-diastolic posterior wall thickness (LVPWs), and fractional shortening (FS) as observed by echocardiography (ISO+MA(PC6) vs. ISO groups: P<0.05). Moreover, evidence from morphological studies demonstrated that acupuncture at PC6 inhibited myocardial hypertrophy and collagen deposition, and normalised the ultrastructural changes. In addition, ANP and TNFα expression were attenuated in the verum acupuncture group compared with the untreated model group (ISO+MA(PC6) vs. ISO groups: P<0.05). Conclusions: The results demonstrated that acupuncture at PC6 attenuates sympathetic overactivity. Additionally, it may improve cardiac performance by reversing adverse cardiac remodelling. Acupuncture has potential as a treatment for sympathetic hypertension.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Eisaku Harada ◽  
Yuji Mizuno ◽  
Makoto Shono ◽  
Hiroyuki Maeda ◽  
Naotsugu Yano ◽  
...  

Introduction: Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and causes substantial morbidity, mortality, and resource utilization in the aging population. The plasma level of B-type natriuretic peptide (BNP) is used as a marker of HF with reduced EF (HFrEF). However, the role of BNP in HFpEF is not well known. The purpose of the present study was to compare the levels of BNP together with the echocardiographic findings between HFpEF and HFrEF. Methods: The study subjects consisted of 1574 patients with HF and early diastolic flow velocity (E)/velocity of early diastolic mitral annular motion (e′) or E/e′≥15 (as a measure of elevated left atrial pressure) (574 men and 1000 women, mean age 78.8±10.7) admitted at our hospital. They were divided into 1238 patients with HFpEF (373 men and 865 women, mean age 79.7±10.2) [left ventricular (LV) EF≥50% and E/e′≥15] and 336 patients with HFrEF (201 men and 135 women, mean age 75.4±11.8) (LVEF<50%). Echocardiographic parameters, age, gender, and BNP were examined. Results: The levels of BNP were lower [107(47, 225) pg/ml vs. 296(121, 626) pg/ml, P<0.001] in the HFpEF group than in the HFrEF group. The frequencies of female gender, age, EF, LV posterior wall thickness were higher (all P<0.001, respectively) and LV mass, LV end-diastolic diameter (LVDd), LV end-systolic diameter (LVDs) and left atrial diameter (LAD) were lower (all P<0.001, respectively) in the HFpEF group than in the HFrEF group. A multiple regression analysis revealed EF (t=-17.0), age (t=11.2), E/e′ (t=10.5), LAD (t=9.0), LV mass (t=7.9), and LVDd (t=-5.3) were independent predictors (all P<0.001, respectively) for the BNP level (P<0.001, R2=0.40) in this order. Conclusions: HFpEF was associated with lower levels of BNP and smaller heart and was more prevalent in the elders and women as compared with HFrEF. Predictors for the levels of BNP were EF, age, and E/e′ in this order. These findings imply that the plasma levels of BNP reflect LVEF more than LV diastolic function (E/e′) and thus are lower in the HFpEF group than in the HFrEF group. These findings suggest that the role of BNP in HF may be different between HFpEF and HFrEF.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y K Taha ◽  
C A Rambart ◽  
F Reifsteck ◽  
R Hamburger ◽  
J R Clugston ◽  
...  

Abstract Background There is a paucity of data describing left ventricular geometry changes in female athletes. While some studies suggest that female athletes participating in dynamic sports exhibit higher prevalence of eccentric left ventricular hypertrophy (LVH) when compared to men, a recent study suggested more concentric geometry changes in female basketball athletes. We were unable to identify studies describing the left ventricular geometry of female collegiate swimmers. Objectives To describe LV geometry changes in a cohort of female collegiate swimmers. Methods We analyzed a cohort of female collegiate swimmers who had a pre-participation cardiac evaluation by 12-lead ECG and 2-dimensional echocardiography. Left ventricular (LV) geometry was assessed based on relative wall thickness (RWT) (defined as: 2 x posterior wall thickness (PWT) divided by LV end-diastolic diameter (LVEDD)) and LV mass (LVM) (Devereux's formula: LVM = [0.8 x 1.04 [(LVEDD + interventricular septum + posterior wall thickness)3 − (LVEDD)3]] + 0.6g) and was indexed to body surface area (BSA).LVH was defined as LV mass index &gt;95 g and was defined as concentric when associated with a relative wall thickness (RWT) &gt;0.42 and as eccentric when RWT was ≤0.42. Concentric remodeling was defined as normal LVM index and increased RWT. Results A total of 83 female collegiate swimmers were included. Their age was 18.5±0.5 years (mean ± standard deviation, SD), 74 (89.2%) were White, BSA was 1.78±0.11 m2, height 173±6.3 cm, weight 66.2±7.2 K. Their interventricular septum diameter was 0.89±0.14 cm, PWT 0.92±0.15 cm, LVEDD 4.9±0.5 cm and LV end-systolic diameter (LVESD) 3.2±0.4 cm. Left atrium diameter ranged from 2.6 to 4.3 cm (mean 3.4 cm ± 0.4 cm). Aortic root diameter ranged from 1.9 to 3.5 cm (mean 2.7±0.3 cm) (Figure 1). LVH was present in 27 swimmers (32.5%). Eccentric LVH was present in 17 athletes (20.5%), concentric hypertrophy in 10 athletes (12%), and concentric remodeling in 12 (14.5%) (Figure 2). No athletes with LVH or concentric remodeling had borderline or abnormal ECG findings based on international criteria. Only two women with normal LV geometry had abnormal ECG findings: prolonged QT interval and abnormal T wave inversion. There was a linear correlation between BSA with LVEDD, LVESD and LV mass (r=0.40, 0.35, and 0.48 with P&lt;0.001,0.002 and &lt;0.001, respectively). However, there was no statistically significant difference between LV geometry groups based on BSA or blood pressure. Conclusion Our data document a high incidence of eccentric hypertrophy among female collegiate swimmers. Concentric remodeling and hypertrophy were also relatively high. Differentiating physiologic from pathologic cardiac remodeling in these athletes is critical to prevent potential complications such as sudden cardiac death, arrhythmias, and other adverse outcomes. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported in part by the American Medical Society for Sports Medicine (AMSSM) Foundation Research Grant 2016 awarded to KE, and the University of Florida REDCap uses the NIH National Center for Advancing Translational Sciences (NCATS) grant UL1 TR001427. Figure 1 Figure 2. LV geometry in female swimmers


2020 ◽  
Vol 19 (2) ◽  
pp. 181-187
Author(s):  
Jing Li ◽  
Yun Zhang ◽  
Weizhong Huangfu ◽  
Yuhong Ma

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.


2018 ◽  
Vol 9 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Jiahui Li ◽  
Aili Li ◽  
Jiali Wang ◽  
Yu Zhang ◽  
Ying Zhou

Purpose: Cardiac valve calcification (VC) is very common in patients on hemodialysis. However, the definite effect of VC on left ventricular (LV) geometry and function in this population is unknown, especially when LV ejection fraction (LVEF) is normal. The aim of this study was to determine the effect of VC on LV geometry and function in long-term hemodialysis patients by conventional echocardiography and two-dimensional speckle tracking echocardiography (2D-STE). Methods: A total of 47 hemodialysis patients (2–3 times weekly for 5 years or more) were enrolled in this study. Cardiac VC was defined as bright echoes of more than 1 mm on one or more cusps of the aortic valve or mitral valve or mitral annulus using echocardiography as the screening method. LV longitudinal global strain (GLS) was assessed on the apical four-chamber view and calculated as the mean strain of 6 segments. LV global circumferential strain was acquired on the LV short axis view at the level of papillary muscles. Results: Twenty-five patients with VC had higher mean values of interventricular septum thickness, LV posterior wall thickness, LV mass index, relative wall thickness, and LV mass/end-diastolic volume than 22 patients without VC (p < 0.05, respectively), indicating more obvious LV hypertrophy (LVH). VC patients had higher mitral annular E/E′ values, especially at the septal side representing increased LV filling pressure compatible with diastolic dysfunction, while only the E/E′ ratio of the septal side was significantly different between the 2 groups (16.7 ± 4.1 vs. 12.3 ± 4.4, p < 0.01). When assessed by GLS, LV longitudinal systolic function was also lower in in patients with VC compared with those without VC (–0.18 ± 0.03 vs. –0.25 ± 0.04; p < 0.01). Conclusions: Cardiac VC diagnosed by echocardiography when it occurs in long-term hemodialysis patients may indicate more severe LVH, myocardial damage, and worse heart function in comparison to those without VC. Tissue Doppler imaging and 2D-STE can detect the subtle change of heart function in this population in the early stage of LV dysfunction when LVEF is normal.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Aldujeli ◽  
J Laukaitiene ◽  
R Unikas

Abstract Background Regular physical exercise causes a continuous gradual increase of the cardiac left ventricular (LV) mass known as physiological adaptive hypertrophy. The extent of LV remodeling depends on the type, amount, and intensity of the exercise. Purpose The aim of this study was to compare structural changes of the heart among Lithuanian football, basketball players and unathletic controls. Methods A total of 50 Lithuanian males aged between 20-29 years volunteered to participate in the study. Football players (n = 15) playing for local II league football clubs,and Basketball players (n = 15) playing for local minor league basketball teams. All athletes had been regularly engaged in their sport for at least three years. Inactive healthy volunteers (n = 20) of similar age served as controls. Routine transthoracic echocardiographic examinations to measure end-diastolic LV dimensions were performed by cardiology fellow under the supervision of a fully licensed cardiologist. Statistical analyses were performed using the SPSS 20.0 software. The value of p &lt; 0,05 was considered as statistically significant. Results No structural or functional pathologies were evident during the echocardiographic examination in any of the subjects. Absolute interventricular septum (IVS) thickness and LV posterior wall thickness, but not LV diameter, were higher in athletes than in inactive controls (P &lt; 0,001). Indexed LV diameter was higher in football players as compared with non-athlete controls and basketball players (P &lt; 0,05). Left ventricular mass of all athletes were higher as compared with controls (p &lt; 0.001). Relative wall thickness was not increased in football players but was higher in basketball players as compared with controls (p &lt; 0.05). Conclusion Cardiac remodeling in Lithuanian football players resulted in left ventricle eccentric hypertrophy due to the LV dilation, increased LV mass and relatively normal relative wall thickness. However in Lithuanian basketball players we noticed an increase in both relative wall thickness and LV mass resulting in LV concentric hypertrophy. Echocardiographic characteristics Groups n End-diastolic LV diameter(mm) End-diastolic Interventricular septum (mm) End-diastolic LV posterior wall LV mass Football Players 15 56.9 10.8 10.8 242 Basketball players 15 53.6 11.5 11.3 254 Inactive individuals 20 53.2 9.1 9.5 182 P value 0.01 &lt;0.001 &lt;0.001 &lt;0.01 Abstract P955 Figure.


1979 ◽  
Vol 57 (s5) ◽  
pp. 55s-57s ◽  
Author(s):  
H. Larkin ◽  
D. C. Johnson ◽  
S. N. Hunyor ◽  
P. Caspari ◽  
R. Kaplan

1. A comparison of direct measurement and M-mode echocardiography in the determination of posterior left ventricular wall thickness was performed in 26 subjects, of whom 21 underwent cardiac bypass surgery; the remainder came to necropsy. 2. In the surgical group a close correlation was demonstrated between direct measurement of posterior wall thickness and the echocardiographic end-diastolic dimension (r = 0·76, P &lt; 0·001). 3. The necropsy measurement of posterior wall thickness correlated with the echocardiographic end-systolic dimension (r = 0·99, P &lt; 0·001). 4. These findings confirm that the echocardiographic measurement of posterior wall thickness accurately reflects the anatomical dimension.


2007 ◽  
Vol 31 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Junwu Mu ◽  
Dawei Qu ◽  
Agata Bartczak ◽  
M. James Phillips ◽  
Justin Manuel ◽  
...  

We hypothesized that cardiac dysfunction was responsible for the high perinatal lethality that we previously reported in fibrinogen-like protein 2 ( Fgl2) knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left ventricular (LV) cardiac structure and function during development in Fgl2 KO and wild-type (WT) mice. The only deaths observed between embryonic day (E)8.5 (onset of heart beating) and postnatal day (P)28 (weaning) were within 3 days after birth, when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments suggested that death was due to acute congestive cardiac failure without evidence of valvular or other obvious cardiac structural abnormalities. Heart rates in Fgl2 KO embryos were significantly reduced at E8.5 and E17.5, and irregular heart rhythms were significantly more common in Fgl2 KO (21/26) than WT (2/21) embryos at E13.5. Indexes of systolic and/or diastolic cardiac function were also abnormal in KO mice at E13.5 and E17.5, in postnatal mice studied at P1, and in KO mice surviving to P28. M-mode analysis showed no difference in LV diastolic chamber dimension, although posterior wall thickness was thinner at P7 and P28 in Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious structural cardiac defects but is associated with a high incidence of neonatal death as well as contractile dysfunction and rhythm abnormalities during embryonic and postnatal development in mice.


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