Evidence for differences in cultured left ventricular fibroblast populations isolated from spontaneously hypertensive and Wistar???Kyoto rats

Klett, Christoph; Palmer, Abraham A.; Dirig, David M.; Gallagher, Ann-Marie; Riosecco-camacho, Natalia; Printz, Morton P.

doi:10.1097/00004872-199512000-00008

Cited by 15 publications

(16 citation statements)

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“…Therefore, primary cultures of WKY and SHR fibroblasts obtained from animals before the f 3-month stage represent an excellent system for testing the C-RAS model. As predicted by this model, SHR cells show elevated levels of mRNA for ATN, ACE, and a-SM actin, lower AT 1 receptor density, enhanced expression of integrins, and increased collagen production compared to WKY cells [5,8,14,15]. Moreover, as discussed previously, all of these changes can be observed in cultured WKY cells by treating them with exogenous Ang II [5][6][7][8].…”

Section: Introductionsupporting

confidence: 64%

“…These are organized into well known structures like filopodia, ruffling lamellae and stress fibers that originate and end at focal adhesions and focal contacts. As mentioned above, SHR cells express more a-SM actin than WKY cells and furthermore, Ang II increases this expression in both WKY and SHR cells [5]. The abundance of a-SM actin, the isoform typically associated with myofibroblasts and smooth muscle cells, suggests that one might expect higher contractile activity in SHR cells and that this higher activity might be associated with the pathogenesis of HHD.…”

Section: Introductionmentioning

confidence: 85%

“…Cardiac fibroblasts express a high density of Ang II receptors [5] and respond in many different ways when stimulated with Ang II. For instance, Ang II stimulates cardiac fibroblast to produce more extracellular matrix (ECM) [6,7], express more alpha-smooth muscle actin (a-SM actin) [5], increase their adhesion to the surrounding ECM by upregulating their integrin expression [7,8] and increase the rate at which they compact artificial collagen gels [9,10]. All of these results are receptor specific since they can be blocked by several competitive inhibitors of the Ang II receptor.…”

Section: Introductionmentioning

confidence: 99%

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Demonstration of altered fibroblast contractile activity in hypertensive heart disease

Marganski

Biase

Burgess

et al. 2003

Cardiovascular Research

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Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Demonstration of altered fibroblast contractile activity in hypertensive heart disease

Marganski

Biase

Burgess

et al. 2003

Cardiovascular Research

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“…Obviously, the present study does not explore the pathophysiology of the possible link between genetic predisposition to hypertension, hyperinsulinemia, and diastolic dysfunction. However, taking into account experimental studies demonstrating that LV fibroblasts from spontaneously hypertensive rats differ from fibroblasts isolated from normotensive Wistar-Kyoto rats in many aspects, such as growth rate in culture, expression of angiotensin II receptors, structure, and steroid responsiveness, 40 we could hypothesize that genetic predisposition to hypertension also influences the response of the fibroblasts to the promoting effect of insulin on collagen production, increasing interstitial collagen accumulation in the myocardial wall.…”

Section: Discussionmentioning

confidence: 99%

Insulin and Diastolic Dysfunction in Lean and Obese Hypertensives

et al. 1999

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Abstract-We investigated the influence of genetic predisposition to hypertension by studying the relation between insulin sensitivity and left ventricular (LV) mass and function in untreated lean and obese hypertensives. We selected 50 lean hypertensives with normotensive parents (negative family history of hypertension [FϪ]), 64 lean hypertensives with 1 or both parents hypertensive (positive family history of hypertension [Fϩ]), 40 obese FϪ hypertensives, and 43 obese Fϩ hypertensives. The 4 groups were comparable regarding age, gender, 24-hour blood pressure profile, and known duration of hypertension. We measured glucose, insulin, and C-peptide during fasting and during an oral glucose tolerance test; LV morphology and function were assessed by digitized M-mode echocardiography. Glucose (fasting and test) levels were normal in all and similar among the 4 groups. Insulin and C-peptide (fasting and stimulated) levels were higher in obese hypertensives than in lean hypertensives; at similar body mass index, insulin and C-peptide levels were higher in Fϩ than in FϪ groups. Compared with lean hypertensives, obese hypertensives had greater LV mass index; LV systolic function was normal in all and similar among the groups. The indices of LV diastolic function were significantly lower in Fϩ than in FϪ groups. LV mass index did not correlate with metabolic parameters; the indices of LV diastolic function were inversely correlated with insulin area during test in only the 2 Fϩ groups. In conclusion, genetic predisposition to hypertension is associated with a reduced insulin sensitivity and affects the response of the myocardium to increased insulin levels, inducing a greater impairment of diastolic function. Insulin sensitivity and genetic predisposition to hypertension seem to have no influence on LV mass. (Hypertension. 1999;34:1208-1214.)Key Words: insulin Ⅲ diastole Ⅲ hypertension, essential Ⅲ obesity Ⅲ hypertrophy E ssential hypertension and obesity are often associated, and each one, per se, can induce myocardial hypertrophy and left ventricular (LV) diastolic dysfunction. 1-5 Insulin resistance and hyperinsulinemia have been described in both hypertension and obesity. 6,7 In experimental studies, insulin has been demonstrated to exert a growth-stimulating effect on cardiomyocytes and to increase collagen production in fibroblasts 8 -12 ; therefore, clinical studies have evaluated the possible contribution of insulin resistance and hyperinsulinemia to the development of myocardial hypertrophy and diastolic dysfunction in hypertension and in obesity and have obtained conflicting results. [13][14][15][16][17][18][19][20] Recently, it has been suggested that genetic factors play an important role in the link between insulin resistance, hypertension, and obesity. In fact, a reduced insulin sensitivity has been demonstrated in lean and obese normotensives and hypertensives with hypertensive parents (positive family history of hypertension [Fϩ]) compared with offspring of normotensive parents (negative family history...

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“…Slides were then stained with freshly prepared oil red o stain for 15 min (Klett et al 1995). After rinsing with 60% isopropanol, nuclei were lightly stained by hematoxylin.…”

Section: Histologymentioning

confidence: 99%

Age-related cardiac muscle sarcopenia: Combining experimental and mathematical modeling to identify mechanisms

Lin

Lopez

Jin³

et al. 2008

Experimental Gerontology

100

109

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Age-related skeletal muscle sarcopenia has been extensively studied and smooth muscle sarcopenia has been recently described, but age-related cardiac sarcopenia has not been previously examined. Therefore, we evaluated adult (7.5±0.5 months; n=27) and senescent (31.8±0.4 months; n=26) C57BL/6J mice for cardiac sarcopenia using physiological, histological, and biochemical assessments. Mice do not develop hypertension, even into senescence, which allowed us to decouple vascular effects and monitor cardiac-dependent variables. We then developed a mathematical model to describe the relationship between age-related changes in cardiac muscle structure and function. Our results showed that, compared to adult mice, senescent mice demonstrated increased left ventricular (LV) end diastolic dimension, decreased wall thickness, and decreased ejection fraction, indicating dilation and reduced contractile performance. Myocyte numbers decreased, and interstitial fibrosis was punctate but doubled in the senescent mice, indicating reparative fibrosis. Electrocardiogram analysis showed that PR interval and QRS interval increased and R amplitude decreased in the senescent mice, indicating prolonged conduction times consistent with increased fibrosis. Intracellular lipid accumulation was accompanied by a decrease in glycogen stores in the senescent mice. Mathematical simulation indicated that changes in LV dimension, collagen deposition, wall stress, and wall stiffness precede LV dysfunction. We conclude that age-related cardiac sarcopenia occurs in mice and that LV remodeling due to increased end diastolic pressure could be an underlying mechanism for age-related LV dysfunction.

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Evidence for differences in cultured left ventricular fibroblast populations isolated from spontaneously hypertensive and Wistar???Kyoto rats

Cited by 15 publications

References 0 publications

Demonstration of altered fibroblast contractile activity in hypertensive heart disease

Demonstration of altered fibroblast contractile activity in hypertensive heart disease

Insulin and Diastolic Dysfunction in Lean and Obese Hypertensives

Age-related cardiac muscle sarcopenia: Combining experimental and mathematical modeling to identify mechanisms

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