The effect of nicotinic acid and pentaerythritoltetranicotinate upon experimental atherosclerosis in the rabbit

Brattsand, Ralph; Lundholm, Lennart

doi:10.1016/0021-9150(71)90041-4

Cited by 25 publications

(5 citation statements)

References 21 publications

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“…Shortly after the discovery of the cholesterol-lowering effect of nicotinic acid by Altschul, its antiatherosclerotic effect was first observed in rabbits (3). Later, a reduction in atherosclerotic lesion size was also seen in other experimental animal models in response to nicotinic acid and its derivatives (4)(5)(6)(7). The first evidence for antiatherosclerotic effects of nicotinic acid in humans came from angiographic studies showing regression of atherosclerosis in coronary and peripheral arteries under nicotinic acid treatment (8,9).…”

Section: Introductionmentioning

confidence: 93%

Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells

Lukasova¹,

Malaval²,

Gille³

et al. 2011

J. Clin. Invest.

226

199

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Nicotinic acid (niacin) is a drug used to reduce the progression of atherosclerosis. Its antiatherosclerotic activity is believed to result from lipid-modifying effects, including its ability to decrease LDL cholesterol and increase HDL cholesterol levels in plasma. Here, we report that in a mouse model of atherosclerosis, we found that nicotinic acid inhibited disease progression under conditions that left total cholesterol and HDL cholesterol plasma levels unaffected. The antiatherosclerotic effect was not seen in mice lacking the receptor for nicotinic acid GPR109A. Surprisingly, transplantation of bone marrow from GPR109A-deficient mice into atherosclerosis-prone animals also abrogated the beneficial effect of nicotinic acid. We detected expression of GPR109A in macrophages in atherosclerotic plaques. In macrophages from WT mice, but not from GPR109A-deficient animals, nicotinic acid induced expression of the cholesterol transporter ABCG1 and promoted cholesterol efflux. Furthermore, activation of GPR109A by nicotinic acid inhibited MCP-1-induced recruitment of macrophages into the peritoneal cavity and impaired macrophage recruitment to atherosclerotic plaques. In contrast with current models, our data show that nicotinic acid can reduce the progression of atherosclerosis independently of its lipid-modifying effects through the activation of GPR109A on immune cells. We conclude therefore that GPR109A mediates antiinflammatory effects, which may be useful for treating atherosclerosis and other diseases.

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Section: Introductionmentioning

confidence: 93%

Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells

Lukasova¹,

Malaval²,

Gille³

et al. 2011

J. Clin. Invest.

226

199

View full text Add to dashboard Cite

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“…In animals, nicotinic acid has a prophylactic effect in experimental atherosclerosis/· 6 Opinions on the therapeutic value of nicotinic acid in obstructive and atherosclerotic vascular diseases are divided, however. Ost and Stenson 24 showed that, after prolonged treatment with high doses, an arteriographically visible regression of an obstruction in the popliteal artery occurred in some patients with intermittent claudication.…”

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confidence: 98%

The relationship between the plasma concentration of free nicotinic acid and some of its pharmacologic effects in man

Svedmyr

Harthon

Lundholm

1969

Clin Pharma and Therapeutics

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“…At the dose of 100mgkg-1, nicotinic acid induces less than 20% lowering of cholesterol while the effect of LG 13979 is constantly around or above 30% and at its peak activity exceeds 50%. The normolipaemic rat model is perhaps not the most suitable for evaluating the hypolipaemic effects of certain nicotinic derivatives such as niceritrol and sorbinicate, for in other laboratory animals (rabbits on an atherogenic diet) these derivatives exhibited an activity equal to or greater than that of nicotinic acid itself (Subissi et a1 1980b;Brattsand & Lundholm 1971), whilst in our experiments they proved less active. This may be due in part to major pharmacokinetic differences of niceritrol (Hattori et a1 1975;Harthon & Brattsand 1979) and sorbinicate (Subissi et a1 1980a) in the various animal species .…”

Section: Discussionmentioning

confidence: 56%

Acute effects on plasma lipids in the rat of a new long-acting nicotinic acid derivative: LG 13979

Subissi¹,

Criscuoli²,

Biagi³

et al. 1983

Journal of Pharmacy and Pharmacology

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The effects on plasma lipids and nicotinic acid concentrations of a single dose of 2-(3-pyridinecarbonylamino)-2-deoxy-1,3,4,6 dihydrogen-D-glucose tetra-3-pyridinecarboxylate (LG 13979) compared with the effects of nicotinic acid and of its known derivatives niceritrol and sorbinicate, at the same doses, were studied in the fasted rat. Results show that LG 13979 has more prolonged activity on plasma free fatty acids and triglycerides, with longer lasting and more intense activity on plasma cholesterol than these three reference standards. Free fatty acid rebound occurs after administration of nicotinic acid and niceritrol, but not after LG 13979. This pharmacodynamic profile may be explained on the basis of the kinetics of nicotinic acid plasma concentrations, which are low, constant and lasting after LG 13979 administration.

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The effect of nicotinic acid and pentaerythritoltetranicotinate upon experimental atherosclerosis in the rabbit

Cited by 25 publications

References 21 publications

Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells

Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells

The relationship between the plasma concentration of free nicotinic acid and some of its pharmacologic effects in man

Acute effects on plasma lipids in the rat of a new long-acting nicotinic acid derivative: LG 13979

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