Pinolenic Acid, a Fatty Acid Derived from Pine Nuts, Found to Suppress Excessive Coronary Artery Contraction

Research Background and Findings 

Coronary arteries are essential blood vessels that deliver oxygen and nutrients to the heart muscle. Excessive contraction of these arteries narrows the vascular lumen and reduces blood flow to the heart. This condition, known as coronary artery spasm, is involved in the development of ischemic heart diseases such as angina pectoris and myocardial infarction.

When platelet activation, endothelial dysfunction, or inflammation occurs, bioactive substances such as thromboxane A₂ (TXA₂) can increase and cause excessive contraction of coronary arteries. TXA₂ stimulates the prostanoid TP receptor expressed in vascular smooth muscle cells, leading to an increase in intracellular calcium concentration and promoting vascular contraction. Therefore, appropriately suppressing TP receptor activity is considered important for preventing excessive contraction of coronary arteries.

The research group previously reported that γ-linolenic acid and α-linolenic acid, fatty acids found in plant oils, inhibit TP receptor–mediated contraction of coronary arteries. Pinolenic acid is a fatty acid abundant in pine nut oil and has a structure similar to those of γ-linolenic acid and α-linolenic acid. However, its effects on coronary artery contraction had not been clarified.

In the present study, the researchers examined the effects of pinolenic acid using porcine coronary arteries. Pinolenic acid concentration-dependently inhibited coronary artery contraction induced by U46619, a drug that selectively stimulates the TP receptor. Pinolenic acid also inhibited contraction induced by prostaglandin F_2α (PGF_2α), which mainly contracts porcine coronary arteries through the TP receptor. In contrast, pinolenic acid showed no clear inhibitory effect on contractions induced by high potassium chloride, acetylcholine, histamine, serotonin, or endothelin-1. These results indicate that pinolenic acid does not broadly suppress vascular contraction in a nonspecific manner, but rather selectively inhibits contraction mediated by the TP receptor.

Pharmacological analysis further suggested that pinolenic acid may act by competing at the receptor with substances that stimulate the TP receptor. This finding is consistent with the possibility that pinolenic acid acts as a competitive antagonist at the TP receptor. In cells expressing the human TP receptor, pinolenic acid significantly suppressed the increase in intracellular calcium concentration induced by TP receptor stimulation. In addition, computational analysis using the three-dimensional structure of the human TP receptor suggested that pinolenic acid may enter the ligand-binding pocket of the receptor. An overview of these findings is shown in Figure 1. Pinolenic acid may alleviate excessive coronary artery contraction by suppressing the activity of the TP receptor, which functions as a “switch” for blood vessel contraction.

This study is the first to demonstrate that pinolenic acid suppresses TP receptor–mediated coronary artery contraction. Because TP receptor activation is involved in the development of ischemic heart disease through the induction of coronary artery spasm, these findings provide important insight into the possible cardiovascular protective actions of plant-derived fatty acids.

The study also confirmed the action of pinolenic acid in cells expressing the human TP receptor, showing that pinolenic acid can act on the human receptor. On the other hand, it remains unclear whether ingestion of pinolenic acid in humans can suppress excessive coronary artery contraction. In addition, information regarding the blood concentration and pharmacokinetics of pinolenic acid after intake remains limited. Further studies, including pharmacokinetic analyses and experiments using more physiologically relevant models, will be needed to determine whether pinolenic acid could serve as a functional food component useful for cardiovascular disease prevention.

Figure 1. Pinolenic acid may suppress the TP receptor and alleviate abnormal coronary artery contraction