Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Nov 1;31(11):1496-1511.
doi: 10.5551/jat.RV22025. Epub 2024 Aug 22.

Fibroblast Growth Factors in Cardiovascular Disease

Hideaki Morita  1 , Masaaki Hoshiga  1
Affiliations
Review

Fibroblast Growth Factors in Cardiovascular Disease

Hideaki Morita et al. J Atheroscler Thromb. .

Abstract

Despite advancements in managing traditional cardiovascular risk factors, many cardiovascular diseases (CVDs) persist. Fibroblast growth factors (FGFs) have emerged as potential diagnostic markers and therapeutic targets for CVDs. FGF1, FGF2, and FGF4 are primarily used for therapeutic angiogenesis. Clinical applications are being explored based on animal studies using approaches such as recombinant protein administration and adenovirus-mediated gene delivery, targeting patients with coronary artery disease and lower extremity arterial disease. Although promising results have been observed in animal models and early-stage clinical trials, further studies are required to assess their therapeutic potential. The FGF19 subfamily, consisting of FGF19, FGF21, and FGF23, act via endocrine signaling in various organs. FGF19, primarily expressed in the small intestine, plays important roles in glucose, lipid, and bile acid metabolism and has therapeutic potential for metabolic disorders. FGF21, found in various tissues, improves glucose metabolism and insulin sensitivity, suggesting potential for treating obesity and diabetes. FGF23, primarily secreted by osteocytes, regulates vitamin D and phosphate metabolism and serves as an important biomarker for chronic kidney disease and CVDs. Thus, FGFs holds promise for both therapeutic and diagnostic applications in metabolic and cardiovascular diseases. Understanding the mechanisms of FGF may pave the way for novel strategies to prevent and manage CVDs, potentially addressing the limitations of current treatments. This review explores the roles of FGF1, FGF2, FGF4, and the FGF19 subfamily in maintaining cardiovascular health. Further research and clinical trials are crucial to fully understand the therapeutic potential of FGFs in managing cardiovascular health.

Keywords: Atherosoclerosis; Cardiometabolic regulation; Cardiovascular disease; Fibroblast growth factors.

PubMed Disclaimer

Conflict of interest statement

No potential conflicts of interest were disclosed.

Figures

Fig.1. Classification of fibroblast growth factors (FGFs)
Fig.1. Classification of fibroblast growth factors (FGFs)
The figure illustrates the classification of the fibroblast growth factor (FGF) family into three main functional groups: paracrine FGFs, endocrine FGFs and intracellular FGFs. Paracrine FGFs (Yellow): These FGFs function primarily through local cell signaling and are categorized into five subfamilies: FGF1 subfamily includes FGF1 and FGF2; FGF4 subfamily includes FGF4, FGF5, and FGF6; FGF7 subfamily includes FGF3, FGF7, FGF10, and FGF22; FGF8 subfamily includes FGF8, FGF17, and FGF18; FGF9 subfamily includes FGF9, FGF16, and FGF20. Endocrine FGFs (Red): These FGFs are involved in systemic signaling and are part of the FGF19 subfamily. This function group includes FGF19, FGF21, and FGF23. Intracellular FGFs (Blue): These FGFs function within the cell and are part of FGF11 subfamily. This functional group includes FGF11, FGF12, FGF13, and FGF14.
Fig.2. Regulation and effects of FGF19
Fig.2. Regulation and effects of FGF19
FGF19 is primarily synthesized and secreted by the small intestine in response to bile acid stimulation. Bile acids in the intestine activates the farnesoid X receptor (FXR), inducing the expression of FGF19.
Fig.3. Regulation and effects of FGF21
Fig.3. Regulation and effects of FGF21
FGF21 is primarily synthesized and secreted in response to fasting. Fatty acids activate peroxisome proliferator-activated receptors-α (PPAR-α) in the liver and peroxisome proliferator-activated receptors-γ (PPAR-γ) in the pancreas, inducing the expression of FGF21.
Fig.4. Regulation and effects of FGF23
Fig.4. Regulation and effects of FGF23
The effects of FGF23 can be classified into canonical and non-canonical effects. The canonical effects of FGF23 mainly involve the regulation of phosphate and vitamin D metabolism through specific receptors and co-receptor αKlotho. The non-canonical effects of FGF23 are mediated through signaling pathways independent of αKlotho.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, Barengo NC, Beaton AZ, Benjamin EJ, Benziger CP, Bonny A, Brauer M, Brodmann M, Cahill TJ, Carapetis J, Catapano AL, Chugh SS, Cooper LT, Coresh J, Criqui M, DeCleene N, Eagle KA, Emmons-Bell S, Feigin VL, Fernández-Solà J, Fowkes G, Gakidou E, Grundy SM, He FJ, Howard G, Hu F, Inker L, Karthikeyan G, Kassebaum N, Koroshetz W, Lavie C, Lloyd-Jones D, Lu HS, Mirijello A, Temesgen AM, Mokdad A, Moran AE, Muntner P, Narula J, Neal B, Ntsekhe M, Moraes de Oliveira G, Otto C, Owolabi M, Pratt M, Rajagopalan S, Reitsma M, Ribeiro ALP, Rigotti N, Rodgers A, Sable C, Shakil S, Sliwa-Hahnle K, Stark B, Sundström J, Timpel P, Tleyjeh IM, Valgimigli M, Vos T, Whelton PK, Yacoub M, Zuhlke L, Murray C, and Fuster V: Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J Am Coll Cardiol, 2020; 76: 2982-3021 - PMC - PubMed
    1. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, and Ornitz DM: Receptor specificity of the fibroblast growth factor family: the complete mammalian FGF family. J Biol Chem, 2006; 281: 15694-15700 - PMC - PubMed
    1. Ornitz DM and Itoh N: The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol, 2015; 4: 215-266 - PMC - PubMed
    1. Beenken A and Mohammadi M: The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov, 2009; 8: 235-253 - PMC - PubMed
    1. Beenken A and Mohammadi M: The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov, 2009; 8: 235-253 - PMC - PubMed

MeSH terms