Abstract-Physiological and pathological cardiac hypertrophy have directionally opposite changes in transcription of thyroid hormone (TH)-responsive genes, including ␣-and ␤-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca 2ϩ -ATPase (SERCA), and TH treatment can reverse molecular and functional abnormalities in pathological hypertrophy, such as pressure overload. These findings suggest relative hypothyroidism in pathological hypertrophy, but serum levels of TH are usually normal. We studied the regulation of TH receptors (TRs) ␤1, ␣1, and ␣2 in pathological and physiological rat cardiac hypertrophy models with hypothyroid-and hyperthyroid-like changes in the TH target genes, ␣-and ␤-MyHC and SERCA. All 3 TR subtypes in myocytes were downregulated in 2 hypertrophy models with a hypothyroid-like mRNA phenotype, phenylephrine in culture and pressure overload in vivo. Myocyte TR␤1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo. In myocyte culture, TR overexpression, or excess T3, reversed the effects of phenylephrine on TH-responsive mRNAs and promoters. In addition, TR cotransfection and treatment with the TR␤1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TR␤1 to transcription of ␤-MyHC, SERCA, and TR␤1, and TR␣1 to ␣-MyHC transcription and increased myocyte size. We conclude that TR isoforms have distinct regulation and function in rat cardiac myocytes. Changes in myocyte TR levels can explain in part the characteristic molecular phenotypes in physiological and pathological cardiac hypertrophy. (Circ Res. 2001;89:591-598.) Key Words: thyroid hormone receptor Ⅲ physiological and pathological hypertrophy Ⅲ ␣ 1 -adrenergic receptor Ⅲ cardiac myocyte Ⅲ rat C ardiac hypertrophy is sometimes considered a single process that leads invariably to myocardial dysfunction (pathological hypertrophy). However, physiological hypertrophy exists in which cardiac function is maintained or enhanced, including normal cardiac development, exercise training, and thyroid hormone (TH) treatment. Exercise and TH can reverse molecular and functional abnormalities in pathological hypertrophy without decreasing ventricular mass, indicating that physiological and pathological hypertrophy are qualitatively distinct processes. [1][2][3][4][5][6] TH-responsive genes in cardiac muscle include ␣-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca 2ϩ -ATPase (SERCA), which are induced by TH, and ␤-MyHC, which is repressed. 7,8 An intriguing observation is that pathological hypertrophy is characterized by hypothyroid-like changes in these target genes, with decreases in ␣-MyHC and SERCA and increases in ␤-MyHC, a molecular phenotype also called the fetal program. 9 The fact that TH treatment can reverse these genetic changes in some models of pathological hypertrophy is additional evidence for a hypothyroid state, but TH blood levels are usually normal. 3 Conversely, physiological hypertrophy caused by exercise is characterized ...

Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.

Background-Calcineurin may play a pivotal role in the signaling of cardiac hypertrophy; since this hypothesis was first put forward, controversial reports have been published using various experimental models. . Treatment with cyclosporin A completely inhibited the development of LVH in EX rats, but it only partially attenuated the development of LVH in AC4 rats. Conclusions-Calcineurin was activated in exercise-induced physiological LVH and in the developing phase of LVH (AC1), but not in decompensated pressure-overload hypertrophy (AC4). Cyclosporin therapy for the prevention of LVH may be harmful because it does not block the development of pathological hypertrophy but rather that of favorable adaptive hypertrophy.

Insulin resistance is the most essential factor for both heart and skeletal muscle FDG uptake in patients with NIDDM.

To clarify if coronary flow reserve (CFR) is related to insulin resistance or hyperglycemia in normotensive NIDDM, myocardial blood flow (MBF) at baseline and during dipyridamole loading were measured with 13N-ammonia positron-emission tomography. CFR was significantly reduced in NIDDM patients compared with age-matched control subjects. CFR in patients with well-controlled NIDDM was significantly higher than in those with poorly controlled NIDDM, whereas insulin resistance was comparable between the two groups. CFR in NIDDM patients was not related to the degree of insulin resistance. CFR correlated significantly with average fasting glucose concentration and average HbA1c, but not with insulin resistance, age, lipid parameters, or blood pressure. In conclusion, control of blood glucose concentration rather than insulin resistance is most likely related to the reduced CFR in NIDDM.

Abstract-Reduced myocardial vasodilatation (MVD) in hypercholesterolemics without overt coronary stenosis has been reported.However, the status of MVD in hypertriglyceridemics has not yet been clarified. The aim of this study was to investigate whether MVD is impaired in patients with hypertriglyceridemia without overt coronary stenosis. Twenty-three hypertriglyceridemics (10 normocholesterolemic hypertriglyceridemics [HTGs] and 13 mixed combined hyperlipidemics [MCHLs]) and 13 age-matched controls were studied. All patients were proven to have more than one normal coronary artery, as diagnosed by coronary angiography, and those segments that were perfused by anatomically normal coronary arteries were used in the study. Myocardial blood flow (MBF) during dipyridamole (DP) loading and baseline MBF were measured by using positron emission tomography and [13 N]ammonia, after which MVD was calculated. Baseline MBF (mL ⅐ min Ϫ1 ⅐ 100 g Ϫ1) was comparable among HTG (76.0Ϯ26.1), MCHL (77.0Ϯ26.1), and controls (80.3Ϯ38.5). However, MBF during DP loading was significantly lower in MCHL (159Ϯ52.5) than in control subjects (292Ϯ166, PϽ.01), while it was comparable in HTG (202Ϯ104) and controls. MVD was significantly reduced in both HTG (2.70Ϯ1.09, PϽ.05) and MCHL (2.07Ϯ.70, PϽ.01) compared with controls (3.73Ϯ1.14). MVD in MCHLs tended to be reduced compared with that in HTGs, but the difference was statistically insignificant (Pϭ.08). There was a significant relationship between MVD and both plasma triglycerides (rϭϪ.47, PϽ.01) and plasma total cholesterol (rϭϪ.55, PϽ.01). When controls and HTGs were combined, the relationship between MVD and plasma total triglycerides became more prominent (rϭϪ.55, PϽ.05), and the significant relationship between cholesterol level and MVD disappeared. Multivariate regression analysis has revealed that the triglyceride level (Fϭ5.2, PϽ.05) was independently related to MVD (rϭ.69, PϽ.01). In conclusion, MVD was reduced in hypertriglyceridemics in anatomically normal coronary arteries. Hypertriglyceridemia is an independent factor for this abnormality. (Arterioscler Thromb Vasc Biol. 1998;18:294-299.) Key Words: hyperlipidemia Ⅲ hypertriglyceridemia Ⅲ atherosclerosis Ⅲ myocardial vasodilatation Ⅲ PET R educed MVD has been thought to be a factor in coronary stenosis.1 It has been shown that MVD can be altered without evidence of ischemia in hypercholesterolemics 2-4 and that there is a significant inverse relationship between MVD and plasma TG levels in hyperlipidemics without evidence of ischemia. 3,5 In fact, alterations in MVD without overt coronary stenosis have been indicated in a variety of conditions; for example, hypertrophic cardiomyopathy, 6 dilated cardiomyopathy, 7 and diabetes with and without associated hypertension, 8 -10 and in normal segments in patients with myocardial infarction. 11 We have reported a reduced MVD without overt coronary stenosis in patients with hypercholesterolemia. 12However, most recent studies, including our own, involved patients with pure hyperchole...

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