Cardiac myofibroblasts: a novel source of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR

Chintalgattu, Vishnu

doi:10.1016/s0022-2828(03)00006-3

Cited by 106 publications

(76 citation statements)

References 37 publications

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“…In a MI model, a previous study (32) has shown that the in vivo CF phenotype is stable and can be studied in culture up to passage 4. The methodologies presented here are consistent with previous reports examining protein expression and signaling by CFs isolated from rats after MI and studied in culture (3,15,16,30). However, unlike these studies, which examined CFs at early time points (Յ4 wk) post-MI, we examined the long-term effects of MI on AC function and collagen production to understand the role of AC in CF function in the late phase of remodeling.…”

Section: Discussionsupporting

confidence: 71%

Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction

Swaney

Patel²,

Yokoyama³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Swaney JS, Patel HH, Yokoyama U, Lai NC, Spellman M, Insel PA, Roth DM. Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction. Am J Physiol Heart Circ Physiol 293: H3216-H3220, 2007. First published September 14, 2007; doi:10.1152/ajpheart.00739.2007.-Myocardial infarction (MI) results in left ventricular remodeling (e.g., ventricular hypertrophy, dilatation, and fibrosis). Fibrosis contributes to increased myocardial stiffening, impaired ventricular filling and function, and reduced cardiac output. Adenylyl cyclase (AC) expression and activity are reduced in animal models of heart failure. Stimulation of AC can inhibit extracellular matrix production in isolated cardiac fibroblasts; however, a role for reduced AC expression and activity in fibrosis associated with cardiac remodeling after chronic MI has never been determined. We tested the hypothesis that AC expression and activity are reduced in cardiac fibroblasts after chronic (18 wk) MI. Rats underwent coronary artery ligation or sham surgery (control), and echocardiography was used to assess left ventricular remodeling 1, 3, 5, 7, 10, 12, and 18 wk after surgery. Cardiac fibroblasts were isolated from the noninfarcted myocardium and compared for differences in AC activity and collagen synthesis. End-diastolic dimension was increased [control: 0.76 Ϯ 0.02 cm and MI: 1.0 Ϯ 0.02 cm (means Ϯ SE), P Ͻ 0.001] and fractional shortening was decreased (control: 44 Ϯ 2% and MI: 17 Ϯ 2%, P Ͻ 0.001) in MI compared with control rats. Basal and forskolin-stimulated cAMP production were decreased by 90% and 93%, respectively, and AC5/6 expression was decreased 39% in fibroblasts isolated from MI rats compared with sham controls. Serum-stimulated collagen production was increased twofold and forskolin-mediated inhibition of collagen synthesis was reduced in fibroblasts from MI rats compared with controls. Our data demonstrate that AC expression and activity are reduced and collagen production is increased in cardiac fibroblasts of rats after MI.CONGESTIVE HEART FAILURE (CHF) is a leading cause of morbidity and mortality in the United States. CHF was believed to result primarily from systolic dysfunction; however, it is recognized that diastolic dysfunction, or an inability of the heart to fill during diastole, is also an underlying mechanism in many patients with heart failure (29). Myocardial fibrosis, a key contributor to cardiac dysfunction during CHF, reflects hyperplasia and increased deposition of extracellular matrix (ECM) material into the interstitial and perivascular space (5). Exaggerated ECM deposition results in myocardial stiffening and decreased relaxation of the heart, ultimately leading to cardiac dysfunction (19,20).The myocardium is composed of cardiac myocytes and nonmyocytes, which include endothelial cells, vascular smooth muscle cells, and fibroblasts (34). Cardiac fibroblasts (CFs), an abundant cell type in the heart (comprising ϳ2/3 of the total cell population) are responsible for basal ECM ho...

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Section: Discussionsupporting

confidence: 71%

Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction

Swaney

Patel²,

Yokoyama³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…As with other nonendothelial cells (16,19,23,30,47), it can be suggested that urothelial VEGF receptors would enable VEGF to act as a survival factor under harsh conditions. Within this model, enhanced activity of VEGF receptors under inflammatory conditions would provide additional layer of protection for urothelium.…”

Section: Discussionmentioning

confidence: 99%

VEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation

Saban

Backer²,

Backer

et al. 2008

American Journal of Physiology-Renal Physiology

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“…91 Besides cardiomyocytes, cardiac myofibroblasts also represent key cellular components during heart development and disease. Interestingly, these cells also express all the main VEGF-A isoforms, as well as their main receptors KDR and Flt-1, 92 and undergo a proliferative response following VEGF stimulation. However, the exact functional effect of VEGF signaling on cardiac myofibroblasts in vivo still remains to be elucidated.…”

Section: Vegf Beyond Therapeutic Angiogenesismentioning

confidence: 99%

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

2012

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Cardiac myofibroblasts: a novel source of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR

Cited by 106 publications

References 37 publications

Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction

Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction

VEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

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