Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

Dallit Mannheim, Joerg Herrmann, Piero O. Bonetti, Ronit Lavi, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective: Isolated diastolic dysfunction is present in 40% of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC). Methods: Three groups of pigs were studied after 12 weeks of normal (N) diet, HC diet, or HC diet with simvastatin (80. mg/day) treatment. Cardiac function was assessed by electron beam computed tomography (EBCT) and percentage of myocardium occupied by microvessels (myocardial vascular fraction) was calculated by micro-CT. Collagen content was determined by Sirius red staining and confirmed by a quantitative, hydroxyoproline-based assay. Results: Compared with N, LDL serum concentration was higher in HC and HC. +. simvastatin (1.0 ± 0.1 vs. 7.9 ± 1.7 and 9.6 ± 1.2. mmol/L, p< 0.05 for both). Cardiac early diastolic filling was reduced in HC compared with N (102.4 ± 11.3 vs. 151.1 ± 12.1. mL/s; p< 0.05) but restored in HC. +. simvastatin (176.8 ± 21.3. mL/s, p< 0.05 vs. HC). Compared with N, myocardial vascular fraction was higher in HC but not in HC. +. simvastatin (1.98 ± 0.84 vs. 4.48 ± 0.31 and 2.95 ± 0.95%; p< 0.05 for HC vs. N). Myocardial collagen content was higher in HC than in HC. +. simvastatin and N (4.72 ± 1.03 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p< 0.05 for HC vs. N), which was attributable mainly to an increase in collagen III (2.90 ± 0.48 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p< 0.05 for HC vs. N). Conclusions: Simvastatin is able to prevent diastolic dysfunction in experimental HC independent of its lipid lowering effect. This beneficial effect is, at least partially, due to a decrease in myocardial fibrosis and angiogenesis.

Original languageEnglish (US)
Pages (from-to)283-291
Number of pages9
JournalAtherosclerosis
Volume216
Issue number2
DOIs
StatePublished - Jun 2011

Fingerprint

Simvastatin
Hypercholesterolemia
Lipids
Collagen
Staining and Labeling
Diet
Blood Vessels
Fibrosis
X Ray Computed Tomography
Microvessels

Keywords

  • Angiogenesis
  • Diastolic dysfunction
  • Fibrosis
  • Hypercholesterolemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect. / Mannheim, Dallit; Herrmann, Joerg; Bonetti, Piero O.; Lavi, Ronit; Lerman, Lilach O; Lerman, Amir.

In: Atherosclerosis, Vol. 216, No. 2, 06.2011, p. 283-291.

Research output: Contribution to journalArticle

@article{1f14d931bc42461da20bc47ab395e128,
title = "Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect",
abstract = "Objective: Isolated diastolic dysfunction is present in 40{\%} of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC). Methods: Three groups of pigs were studied after 12 weeks of normal (N) diet, HC diet, or HC diet with simvastatin (80. mg/day) treatment. Cardiac function was assessed by electron beam computed tomography (EBCT) and percentage of myocardium occupied by microvessels (myocardial vascular fraction) was calculated by micro-CT. Collagen content was determined by Sirius red staining and confirmed by a quantitative, hydroxyoproline-based assay. Results: Compared with N, LDL serum concentration was higher in HC and HC. +. simvastatin (1.0 ± 0.1 vs. 7.9 ± 1.7 and 9.6 ± 1.2. mmol/L, p< 0.05 for both). Cardiac early diastolic filling was reduced in HC compared with N (102.4 ± 11.3 vs. 151.1 ± 12.1. mL/s; p< 0.05) but restored in HC. +. simvastatin (176.8 ± 21.3. mL/s, p< 0.05 vs. HC). Compared with N, myocardial vascular fraction was higher in HC but not in HC. +. simvastatin (1.98 ± 0.84 vs. 4.48 ± 0.31 and 2.95 ± 0.95{\%}; p< 0.05 for HC vs. N). Myocardial collagen content was higher in HC than in HC. +. simvastatin and N (4.72 ± 1.03 vs. 1.62 ± 0.12 and 1.21 ± 0.24{\%} area staining; p< 0.05 for HC vs. N), which was attributable mainly to an increase in collagen III (2.90 ± 0.48 vs. 1.62 ± 0.12 and 1.21 ± 0.24{\%} area staining; p< 0.05 for HC vs. N). Conclusions: Simvastatin is able to prevent diastolic dysfunction in experimental HC independent of its lipid lowering effect. This beneficial effect is, at least partially, due to a decrease in myocardial fibrosis and angiogenesis.",
keywords = "Angiogenesis, Diastolic dysfunction, Fibrosis, Hypercholesterolemia",
author = "Dallit Mannheim and Joerg Herrmann and Bonetti, {Piero O.} and Ronit Lavi and Lerman, {Lilach O} and Amir Lerman",
year = "2011",
month = "6",
doi = "10.1016/j.atherosclerosis.2011.02.036",
language = "English (US)",
volume = "216",
pages = "283--291",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

AU - Mannheim, Dallit

AU - Herrmann, Joerg

AU - Bonetti, Piero O.

AU - Lavi, Ronit

AU - Lerman, Lilach O

AU - Lerman, Amir

PY - 2011/6

Y1 - 2011/6

N2 - Objective: Isolated diastolic dysfunction is present in 40% of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC). Methods: Three groups of pigs were studied after 12 weeks of normal (N) diet, HC diet, or HC diet with simvastatin (80. mg/day) treatment. Cardiac function was assessed by electron beam computed tomography (EBCT) and percentage of myocardium occupied by microvessels (myocardial vascular fraction) was calculated by micro-CT. Collagen content was determined by Sirius red staining and confirmed by a quantitative, hydroxyoproline-based assay. Results: Compared with N, LDL serum concentration was higher in HC and HC. +. simvastatin (1.0 ± 0.1 vs. 7.9 ± 1.7 and 9.6 ± 1.2. mmol/L, p< 0.05 for both). Cardiac early diastolic filling was reduced in HC compared with N (102.4 ± 11.3 vs. 151.1 ± 12.1. mL/s; p< 0.05) but restored in HC. +. simvastatin (176.8 ± 21.3. mL/s, p< 0.05 vs. HC). Compared with N, myocardial vascular fraction was higher in HC but not in HC. +. simvastatin (1.98 ± 0.84 vs. 4.48 ± 0.31 and 2.95 ± 0.95%; p< 0.05 for HC vs. N). Myocardial collagen content was higher in HC than in HC. +. simvastatin and N (4.72 ± 1.03 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p< 0.05 for HC vs. N), which was attributable mainly to an increase in collagen III (2.90 ± 0.48 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p< 0.05 for HC vs. N). Conclusions: Simvastatin is able to prevent diastolic dysfunction in experimental HC independent of its lipid lowering effect. This beneficial effect is, at least partially, due to a decrease in myocardial fibrosis and angiogenesis.

AB - Objective: Isolated diastolic dysfunction is present in 40% of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC). Methods: Three groups of pigs were studied after 12 weeks of normal (N) diet, HC diet, or HC diet with simvastatin (80. mg/day) treatment. Cardiac function was assessed by electron beam computed tomography (EBCT) and percentage of myocardium occupied by microvessels (myocardial vascular fraction) was calculated by micro-CT. Collagen content was determined by Sirius red staining and confirmed by a quantitative, hydroxyoproline-based assay. Results: Compared with N, LDL serum concentration was higher in HC and HC. +. simvastatin (1.0 ± 0.1 vs. 7.9 ± 1.7 and 9.6 ± 1.2. mmol/L, p< 0.05 for both). Cardiac early diastolic filling was reduced in HC compared with N (102.4 ± 11.3 vs. 151.1 ± 12.1. mL/s; p< 0.05) but restored in HC. +. simvastatin (176.8 ± 21.3. mL/s, p< 0.05 vs. HC). Compared with N, myocardial vascular fraction was higher in HC but not in HC. +. simvastatin (1.98 ± 0.84 vs. 4.48 ± 0.31 and 2.95 ± 0.95%; p< 0.05 for HC vs. N). Myocardial collagen content was higher in HC than in HC. +. simvastatin and N (4.72 ± 1.03 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p< 0.05 for HC vs. N), which was attributable mainly to an increase in collagen III (2.90 ± 0.48 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p< 0.05 for HC vs. N). Conclusions: Simvastatin is able to prevent diastolic dysfunction in experimental HC independent of its lipid lowering effect. This beneficial effect is, at least partially, due to a decrease in myocardial fibrosis and angiogenesis.

KW - Angiogenesis

KW - Diastolic dysfunction

KW - Fibrosis

KW - Hypercholesterolemia

UR - http://www.scopus.com/inward/record.url?scp=79958002352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958002352&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2011.02.036

DO - 10.1016/j.atherosclerosis.2011.02.036

M3 - Article

C2 - 21414623

AN - SCOPUS:79958002352

VL - 216

SP - 283

EP - 291

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 2

ER -