1.The role of inflammation in heart failure with preserved ejection fraction.
Qi ZHANG ; Yun-Er CHEN ; Xin-Xin ZHU ; Xia WANG ; Ai-Juan QU
Acta Physiologica Sinica 2023;75(3):390-402
Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.
Humans
;
Heart Failure
;
Stroke Volume/physiology*
;
Hypertrophy, Left Ventricular/metabolism*
;
Ventricular Dysfunction, Left/metabolism*
;
Inflammation/complications*
;
Obesity
;
Hypertension
2.Study of correlation factors with left ventricular hypertrophy during cardiac hypertrophy induced hypertension and regression in rats.
Hai-ying LI ; Zi-quan LIU ; Chang-qing TONG ; Li QI
Chinese Journal of Applied Physiology 2003;19(2):127-130
AIMTo investigate the relations between left ventricular hypertrophy and systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), neuropeptide Y (NPY) during cardiac hypertrophy and regression.
METHODSBlood pressure and heart rate were recorded with polygraph channel biologic message system. NPY in plasma and myocardium were measured with Radioimmunoassay. Correlation coefficient were calculated with SPSS software.
RESULTSThere were positive correlations between SBP, DBP, MAP, NPY in the cardiac tissue and cardiac coefficient (LVW/BW). There was no correlations between cardiac coefficient and heart rate (HR), NPY in plasma.
CONCLUSIONHypertension is one of cardiac hypertrophy factors, SBP correlate better with LVW/ BW than DBP. SBP, DBP, MAP, NPY in cardiac tissue has correlative tendency with LVW/BW.
Animals ; Blood Pressure ; Heart Rate ; Hypertension ; metabolism ; physiopathology ; Hypertrophy, Left Ventricular ; metabolism ; physiopathology ; Male ; Neuropeptide Y ; metabolism ; Rats ; Rats, Wistar
3.Correlation between left ventricular mass index and NADPH oxidase p22phox in patients with non-valvular chronic heart failure.
Shuguo YANG ; Zongqin YAO ; Min LI ; Runsheng YOU ; Aihong WANG ; Hongjin ZHAO
Journal of Southern Medical University 2013;33(1):142-144
OBJECTIVETo study the correlation between the expression levels of phagocytic NADPH oxidase p22phox subunit and left ventricular mass index (LVMI) in patients with non-valvular chronic heart failure and explore the role of oxidative stress caused by NADPH oxidase p22phox subunit in left ventricular remodeling.
METHODSSemi-quantitative RT-PCR was used to examine the expression levels of phagocytic NADPH oxidase p22phox in 59 patients with non-valvular chronic heart failure and 20 control subjects. All the subjects underwent ultrasonic cardiography to record their IVST, LVPWT, LVEDd, LVEDs, and EF. Based on the calculated LVMI, the patients were divided into heart failure without LV hypertrophy (LVH) group and heart failure with LVH group.
RESULTSThe patients with heart failure showed significantly higher expression of phagocytic NADPH oxidase p22phox than the control subjects (0.91∓0.37 vs 0.68∓0.33, P=0.039), and the patients with LVH had significantly higher p22phox expression than those without LVH (1.58∓0.20 vs 0.71∓0.24, P=0.026). LVMI showed a positive correlation with the expression of p22phox in these patients (r=0.508, P<0.05).
CONCLUSIONNADPH oxidase p22phox expression level is positively correlated with LVMI and can be indicative of the level of left ventricular remodeling in patients with non-valvular chronic heart failure.
Adult ; Aged ; Case-Control Studies ; Female ; Heart Failure ; metabolism ; physiopathology ; Humans ; Hypertrophy, Left Ventricular ; metabolism ; physiopathology ; Male ; Middle Aged ; NADPH Oxidases ; metabolism ; Ventricular Remodeling
4.Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats.
Xiao-Li DING ; Qing-Qing YUAN ; Ding-Jia XUE ; Fu-Ming YANG ; Yi-Zhun ZHU ; Hai-Bing QIAN
China Journal of Chinese Materia Medica 2022;47(2):461-468
To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.
Angiotensin II/metabolism*
;
Animals
;
Cardiomegaly/genetics*
;
Gallic Acid/analogs & derivatives*
;
Hypertrophy, Left Ventricular/pathology*
;
Myocardium/pathology*
;
Rats
5.Upregulation of adrenomedullin system in left ventricular hypertrophy of severe hypertension rats.
Xin WANG ; Nishikimi TOSHIO ; Zhi-zhong LI ; Qing-xiang LI ; Xiao-ling ZHU ; Shu-gong BAI
Chinese Journal of Cardiology 2005;33(1):77-80
OBJECTIVETo investigate the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand and amidating activity in the hypertrophied heart in severe hypertension.
METHODSThe following four groups were studied: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor was converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly was converted to active mature AM (AM-m) by enzymatic amidation. AM-m, AM-total (AM-T; AM-T = AM-m + AM-Gly), atrial natriuretic peptide (ANP) in the plasma and left ventricle (LV) by immunoradiometric assay, and gene expression of AM and ANP were measured.
RESULTSSHR-SP had increased blood pressure, LV weight, plasma and LV ANP levels and mRNA levels of ANP compared with WKY. AM-m and AM-T levels in the plasma (AM-m: +31%; AM-T: +56%) and in the LV (AM-m: +84%; AM-T: +31%) were significantly higher in SHR-SP than those in WKY. The LV tissue AM-m/AM-T ratio was significantly higher in SHR-SP (93.2%) than that in WKY. The mRNA levels of AM in the LV were significantly higher in SHR-SP than those in WKY. Captopril and trichlormethiazide similarly decreased blood pressure and LV hypertrophy with the reduction of the LV AM-m and AM-T levels and mRNA abundance of AM.
CONCLUSIONSThese results suggested that cardiac AM system was upregulated in the hypertrophied heart in this hypertension model. Considering that AM being as an antiremodeling autocrine and(or) paracrine factor, upregulation of the AM system may modulate the pathophysiological course in LV hypertrophy.
Adrenal Glands ; metabolism ; Adrenomedullin ; metabolism ; Animals ; Hypertension ; metabolism ; pathology ; Hypertrophy, Left Ventricular ; metabolism ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Up-Regulation
6.Effect of Salvia miltiorrhiza on left ventricular hypertrophy and cardiac aldosterone in spontaneously hypertensive rats.
Shaojie HAN ; Zhi ZHENG ; Dahong REN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):302-304
Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy (LVH) and its possible mechanism--inhibiting the action of cardiac aldosterone in spontaneously hypertensive rats (SHR) were investigated. Normotensive Wistar-kyoto (WKY) rats and SHRs were used. Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index were measured. Sections of heart tissue were stained with HE method and VanGieson method. Collagen volume fraction was determined in the left ventricle by automatically quantitative morphometry. Cardiac aldosterone concentration was measured by radioimmunoassay. The results indicated that compared with WKY rats, SHRs exhibited higher SBP, left ventricular collagen volume fraction, and aldosterone concentration (all P < 0.05). After the treatment with Salvia Miltiorrhiza, SBP, left ventricular collagen volume fraction, and aldosterone concentration in SHR were decreased as compared with control group (P < 0.05) except SBP. It was concluded that chronic treatment with Salvia Miltiorrhiza could prevent left ventricular hypertrophy in SHR, significantly inhibit collagen compositions in left ventricle. The mechanism was probably related with the inhibition of the cardiac aldosterone action.
Aldosterone
;
metabolism
;
Animals
;
Drugs, Chinese Herbal
;
pharmacology
;
Hypertension
;
metabolism
;
physiopathology
;
Hypertrophy, Left Ventricular
;
metabolism
;
prevention & control
;
Male
;
Myocardium
;
metabolism
;
Rats
;
Rats, Inbred SHR
;
Rats, Inbred WKY
;
Salvia miltiorrhiza
7.Role of calcineurin in the progression of cardiac hypertrophy in renovascular hypertensive rats.
Hong-Zhuan SHENG ; Ji-Nan ZHANG ; Di YANG ; Guo-Ping YANG ; Jin-Dan XU ; Xiang-Jian CHEN
Acta Physiologica Sinica 2003;55(5):594-598
The present study was to investigate the mRNA, protein expression and the activity of calcineurin in the hypertrophic heart, and to determine the effect of calcineurin inhibitor--cyclosporine A (CsA) on the regression of cardiac hypertrophy in renovascular hypertensive rats. Renovascular hypertension was induced by two kidney-one clip methods. Two months after the operation, cardiac hypertrophy was determined by histological analysis performed in some rats (2K1C-2M), then the rats were subdivided into 2 groups: (1) 3-month old two kidney-one clip group (2K1C-3M) with rats receiving 0.9% NaCl per day for one month, and (2) CsA-treated group with rats treated with CsA for one month. Sham-operated rats were used as control. The ratio of the left ventricular weight to tibial length (LVW/TL), the area of cardiac myocyte, mRNA and protein expression and the activity of calcineurin were determined. Both the LVW/TL and the cardiomyocyte area were significantly larger in 2K1C-2M and 2K1C-3M rats than in age-matched sham-operated rats. Treatment with CsA significantly attenuated the increase in the LVW/TL as well as the cardiomyocyte area. The mRNA, protein expression and the activity of calcineurin were significantly higher in 2K1C-2M and 2K1C-3M rats than those in the age-matched sham-operated rats, while the elevation of mRNA, protein expression and activity of calcineurin were significantly suppressed in the CsA-treated rats. In conclusion, calcineurin plays a role in the progression of cardiac hypertrophy in renovascular hypertensive rats. The inhibition of calcineurin can reverse cardiac hypertrophy.
Animals
;
Calcineurin
;
biosynthesis
;
genetics
;
metabolism
;
Cyclosporine
;
pharmacology
;
Hypertension, Renovascular
;
complications
;
metabolism
;
physiopathology
;
Hypertrophy, Left Ventricular
;
etiology
;
metabolism
;
physiopathology
;
RNA, Messenger
;
biosynthesis
;
genetics
;
Rats
;
Rats, Sprague-Dawley
8.Influence of daidzein on left ventricular remodeling in rats with hypertrophic myocardium induced by pressure overload.
Li ZHOU ; Qing ZHOU ; Xiao-qing XIONG ; Jian-xin LIU ; Wei HE
China Journal of Chinese Materia Medica 2007;32(14):1449-1452
OBJECTIVETo investigate the protective effects of daidzein (DD) on ventricular remodeling in rats with myocardial hypertrophy induced by pressure overload and its mechanism.
METHODMyocardial hypertrophy model of rats induced by pressure overload was prepared by constricting abdominal aorta. The operated rats were randomly divided into sham operated control group, aorta-constricted model group and three DD groups (30, 60, 120 mg kg(-1)). Four weeks later, the heart-weight (HW), left ventricular weight (LVW), the ratio of HW/BW and LVW/BW (LVI) and the cardio-myocyte diameters (MD) after dyeing by HE colar were measured. The hydroxyroline, nitric oxide (NO) and the activity of nitric oxide synthetase (NOS) and Na+ -K+ -ATPase, Ca2+ -ATPase in left ventricle were quantified with spectrophotometry and the angiotension II (Ang II) in left ventricle and serum was messured with radioimmunoassay.
RESULTAfter treatment of the left ventricular with DD, vs aorta-contricted model group, NO content, cNOS and Na+ -K+ -ATPase, Ca2+ -ATPase activity were significantly increased, the content of AngII in left ventricle and serum and iNOS activity and the ratio of HW/BW, LVI, MD were significantly reduced.
CONCLUSIONDD has protective effects on ventricular remodeling in rats with myocardial hypertrophy induced by pressure overload and its mechanism may be related to raising NO content and reducing the level of Ang II.
Angiotensin II ; blood ; metabolism ; Animals ; Hypertrophy, Left Ventricular ; metabolism ; pathology ; Isoflavones ; pharmacology ; Male ; Myocardium ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Phytoestrogens ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects
9.Relationships of Blood Pressure Circadian Rhythm and Brain Natriuretic Peptide with Left Ventricular Hypertrophy in the Patients with Primary Hypertension.
Hui-Juan KOU ; Xin WANG ; Deng-Feng GAO ; Xin DONG ; Jin WEI ; Rui MA
Acta Academiae Medicinae Sinicae 2016;38(5):514-521
Objective To investigate the relationships of blood pressure circadian rhythm and brain natriuretic peptide (BNP) with left ventricular hypertrophy (LVH) in patients with primary hypertension. Methods Totally 349 patients (74 with LVH and 275 without LVH) with primary hypertension were enrolled in this study.Echocardiography was performed to determine left ventricular mass index (LVMI) using the Devereux formula. The nocturnal blood pressure decline rate,24-hour blood pressure (24 h PP; especially 24 h mean systolic blood pressure,24 h SBP) and blood pressure index (PPI) were determined by 24 h-ambulatory blood pressure monitoring. These 349 hypertensive patients were divided into four groups including supper-dipper group (defined as≥;20%, n=7),dipper group (defined as 10%- 20%, n=77),non-dipper group (defined as 0- 10%, n=173),and anti-dipper group (defined as<0, n=92). The baseline demographic characteristics of patients were collected. Fasting blood sugar,blood lipids,blood urea nitrogen,serum cretinine,cystatin C,uric acid,and plasma BNP level were measured. Results The patients with LVH (n=74) had significantly higher percentage of grade 3 hypertension (85.1% vs. 46.9%;χ=34.428,P<0.001),24 h SBP (134 mmHg vs. 129 mmHg; t=3.175,P=0.002)(1 mmHg=0.133 kPa),daytime-mean SBP (134 mmHg vs. 130 mmHg; t=2.197,P=0.029),night-mean SBP(132 mmHg vs. 121 mmHg; t=4.763,P<0.001),and 24 h PP(57 mmHg vs. 52 mmHg; t=4.120,P<0.001) and PPI (0.43 vs. 0.41; t=3.335,P=0.001) and lower nocturnal blood pressure decline rate [(1.30±8.02)% vs. (5.68±7.25)%; t=-4.510,P<0.001] than the non-LVH patients (n=275). The LVH hypertensive group had significantly higher BNP level (87.8 pg/ml vs. 28.8 pg/ml; t=2.170,P=0.034) and LVMI (135.1 g/mvs. 88.7 g/m; t=15.285,P<0.001) than the control group. No significant difference was observed in the BNP level among supper-dipper,dipper,non-dipper and anti-dipper groups (P=0.137).However,the difference was statistically significant in the LVMI (P=0.001). Additionally,patients in the anti-dipper group had significantly higher LVMI than those in the dipper patients (100.3 g/mvs. 86.3 g/m; t=4.335,P<0.001) and non-dipper (100.3 g/mvs.93.7 g/m; t=1.987,P=0.048). Patients in the non-dipper group had significantly higher LVMI than those in the dipper group (93.7 g/mvs. 86.3 g/m; t=2.693,P=0.008). The multivariate linear correation analysis and logistic regressions analysis suggested a significant correlation of LVMI with BNP and the grade of hypertension. Conclusion With the increasing of plasma BNP level,the left ventricular hypertrophy is closely related to abnormal blood pressure circadian rhythm and the grade of hypertension in primary hypertensive patients.
Blood Pressure
;
Blood Pressure Monitoring, Ambulatory
;
Circadian Rhythm
;
Echocardiography
;
Essential Hypertension
;
Humans
;
Hypertension
;
physiopathology
;
Hypertrophy, Left Ventricular
;
Natriuretic Peptide, Brain
;
metabolism
10.Effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats.
Li-Hua TAN ; Xiao-Gang LI ; Yun-Zhong GUO ; Xiao-Hong TANG ; Kai YANG ; Wei-Hong JIANG
Journal of Zhejiang University. Medical sciences 2013;42(5):550-555
OBJECTIVETo investigate the effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats.
METHODSThirty six spontaneously hypertensive rats (SHR) were divided into 3 groups with 12 animals in each group: SHR control group,operation group and sham operation group. Bilateral renal sympathectomy or sham operation were performed in operation and sham groups,respectively; another 12 WKY rats served as normal controls. The blood pressure and body weight were examined weekly. The animals were sacrificed at w1 and w6, rat hearts were collected and left ventricular mass index (LVMI) was calculated. The expression of TLR4,TNF-α and IL-6 in heart tissue were detected by immunohistochemistry and Western blot.
RESULTSThe systolic blood pressure [(201.67 ± 11.09) mmHg compared with (140.0 ± 10.86)mmHg,P<0.05],diastolic blood pressure [(144.50 ± 10.48)mmHg compared with (78.50 ± 7.32)mmHg,P<0.05], LVMI (2.44 ± 0.05 compared with 1.93 ± 0.05,P<0.05),the expression of TLR4 (0.298 ± 0.004 compared with 0.126 ± 0.004, P<0.05), NF-κB (0.249 ± 0.006 compared with 0.195 ± 0.005, P<0.05),TNF-α(0.323 ± 0.004 compared with 0.146 ± 0.004,P <0.05), IL-6 (0.283 ± 0.005 compared with 0.207 ± 0.006, P<0.05) in SHR control group were significantly higher than those in WKY group. Compared to sham operation group,the systolic blood pressure (157.30 ± 9.35 compared with 197.30 ± 11.5, P<0.05),diastolic blood pressure (112.50 ± 6.25 compared with 146.80 ± 7.6, P<0.05),LVMI (2.32 ± 0.04 compared with 2.57 ± 0.09, P<0.05, TLR4 (0.198 ± 0.006 compared with 0.317 ± 0.008, P<0.05), NF-κB (0.208 ± 0.006 compared with 0.332 ± 0.007, P<0.05), TNF-α(0.27 ± 0.009 compared with 0.375 ± 0.004,P<0.05), IL-6 (0.218 ± 0.004 compared with 0.376 ± 0.009, P<0.05) in operation group were all decreased at w1 after sympathectomy. Six weeks after the operation,there were no significant differences in systolic blood pressure (197.50 ± 12.13 compared with 208.83 ± 10.23,P>0.05) and diastolic blood pressure (150.33 ± 7.74 compared with 151.50 ± 8.22, P>0.05) between denervated and sham-operated SHRs; however,the LVMI (2.46 ± 0.07 compared with 2.81 ± 0.05,P<0.05) and the expression of TLR4(0.301 ± 0.009 compared with 0.567 ± 0.006, P<0.05), NF-κB (0.251 ± 0.004 compared with 0.476 ± 0.009,P<0.05),TNF-α(0.324 ± 0.005 compared with 0.535 ± 0.006, P<0.05,IL-6 (0.285 ± 0.009 compared with 0.549 ± 0.007, P<0.05) in operation group were still significantly lower than those in sham operation group.
CONCLUSIONRenal sympathetic denervation can significantly delay the progression of LVH in SHR, which may associated with lowering blood pressure and decreasing expression of TLR4, NF-κB,TNF-α, IL-6 in myocardial tissue.
Animals ; Blood Pressure ; Hypertrophy, Left Ventricular ; surgery ; Interleukin-6 ; metabolism ; Kidney ; metabolism ; NF-kappa B ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Sympathectomy ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism